Pharmaceutical preparation comprising an active dispersed on a matrix

ABSTRACT

The present invention relates to the field of pharmaceutical technology and describes a novel advantageous preparation for an active ingredient. The novel preparation is suitable for producing a large number of pharmaceutical dosage forms. In the new preparation an active ingredient is present essentially uniformly dispersed in an excipient matrix composed of one or more excipients selected from the group of fatty alcohol, triglyceride, partial glyceride and fatty acid ester.

TECHNICAL FIELD

The present invention relates to the field of pharmaceutical technologyand describes a novel advantageous preparation for an active ingredient.The novel preparation is suitable for the production of a large numberof pharmaceutical dosage forms.

BACKGROUND ART

In order to achieve particular properties of a dosage form, such as, forexample, taste masking in the case of active ingredients with anunpleasant taste, resistance to gastric juice in the case of acid-labileactive ingredients or controlled release of an active ingredient,normally active ingredient pellets are provided with an appropriatefunctional coating. If such coated pellets are then further processed todosage forms, for example shaped to tablets by compression withexcipients, there is a risk that the coating is damaged and thus thefunctionality is at least partly lost again.

DESCRIPTION OF THE INVENTION

It is an object of the present invention to provide a preparation foractive ingredients which is able to retain a desired functionality andcan be further processed to a large number of pharmaceutical processforms with negligible impairment of a given functionality.

It has now been found, surprisingly, that this object is achieved by apreparation in which an active ingredient is essentially uniformlydispersed in an excipient matrix composed of one or more excipientsselected from the group of fatty alcohol, triglyceride, partialglyceride and fatty acid ester.

The invention therefore relates to a preparation in which an activeingredient is essentially uniformly dispersed in an excipient matrixcomposed of one or more excipients selected from the group of fattyalcohol, triglyceride, partial glyceride and fatty acid ester.

It has further been found that particularly advantageous preparationscan be obtained by adding solid paraffin to the excipient matrix. Theinvention therefore relates further to a preparation in which an activeingredient is essentially uniformly dispersed in an excipient matrixcomposed of at least one solid paraffin together with one or moreexcipients selected from the group of fatty alcohol, triglyceride,partial glyceride and fatty acid ester.

The invention further relates to preparations in which an activeingredient is essentially uniformly dispersed i) in an excipient matrixcomposed of a mixture comprising at least one fatty alcohol and at leastone solid paraffin, ii) in an excipient matrix comprised of a mixturecomprising at least one triglyceride and at least one solid paraffin,iii) In an excipient matrix composed of a mixture comprising at leastone partial glyceride and at least one solid paraffin or iv) in anexcipient matrix composed of a mixture comprising at least one fattyacid ester and at least one solid paraffin.

Further subject matters are evident from the claims.

The preparations for the purpose of the invention preferably comprisenumerous individual units in which at least one active ingredientparticle, preferably a large number of active ingredient particles, ispresent in an excipient matrix composed of the excipients of theinvention (also referred to as active ingredient units hereinafter). Theactive ingredient is preferably essentially uniformly dispersed, inparticular homogeneously dispersed or dissolved, in the excipientmatrix. A preparation preferably comprises microspheres.

The preparations of the invention are distinguished in particular byhigh stability, a release of active ingredient which can be controlledby the particle size and composition of the matrix, good flowcharacteristics, good compressibility and by a uniform delivery ofactive ingredient. In the case of acid-labile active ingredients it ismoreover possible to achieve, through choice of the matrix excipients,an acid resistance so that it is possible in the case of oral forms todispense with an acid-resistant coating (enteric coating). In the caseof active ingredients which have an unpleasant taste or, for example,show a local anesthetic effect in the mouth after administration, it hasbeen observed that an unpleasant taste of the active ingredient can bemasked, and anesthetic effects in the mouth can be avoided, bypreparations of the invention. It is particularly worthy of mention thatthe preparations of the invention can be further processed to a largenumber of pharmaceutical dosage forms without thereby losing a givenfunctionality (such as taste masking, resistance to gastric juice,slowing of release). Thus, for example, on compression of the activeingredient units of the invention no or negligible loss of functionalityis observed even if deformation of the active ingredient units occurs.In contrast to this, with conventional pellets, which normally have afunctional coating (such as taste masking, resistance to gastric juice,slowing of release), a certain degree of damage to the coating and thusto the functionality is observed on further processing to dosage forms,for example on compression to tablets. This may also lead in some casesto active ingredient being released in an unwanted way.

The particle size of the individual units is advantageously less than orequal to 2 mm, preferably 50–800 μm, particularly preferably 50–700 μmand very particularly preferably 50–600 μm. Preference is given tomicrospher s of a particle size of 50–500 μm, particularly preferably of50–400 μm. Particular preference is given to monomodal microspheres witha particle size of 50–400 μm, particularly of 50–200 μm.

Active ingredients of the invention are, in particular, activepharmaceutical ingredients. Examples of active ingredients which mayform part of the preparations of the invention are, in particular, theactive pharmaceutical ingredients mentioned below:

Adrenergics:

apraclonidine; brimonidine; dapiprazole; deterenol; dipivefrin;dopamine; ephedrine; esproquin; etafedrine; hydroxyamphetamine;levonordefrin; metaraminol; norepinephrine; oxidopamine;phenylpropanolamine; prenalterol; propylhexedrine; pseudoephedrine.

Adrenocorticosteroids:

ciprocinonide; desoxycorticosterone acetate; desoxycorticosteronepivalate; dexamethasone acetate; fludrocortisone acetate; flumoxonide;hydrocortisone hemisuccinate; methylprednisolone hemisuccinate;naflocort; procinonide; timobesone acetate; tipredane.

Agents to Prevent Alcohol Abuse:

disulfiram, acamprosate, milnacipran, fomepizole, lazabemide, nadide;nitrefazole; sunepitron.

Aldosterone Antagonists:

canrenoate; canrenone; dicirenone; mexrenoate; prorenoate;spironolactone, epostane, mespirenone; oxprenoate, spirorenone,spiroxasone, prorenone, eplerenone.

Amino Acids:

alanine; aspartic acid; cysteine; histidine; isoleucine; leucine;lysine; methionine; phenylalanine; proline; serine; threonine;tryptophan; tyrosine; valine.

Active Ingredients for Ammonium Detoxification:

arginine; arginine glutamate; arginine hydrochloride; glutamic acid;

Anabolics:

androstanolone, bolandiol diproplonate; bolasterone; boldenoneundecylenate; bolenol; bolnantalate; ethylestrenol; metenolone acetate;metenolone enanthate; bolazine; mesteronole; metandienone; nandrolone;oxandrolone; prasterone; stanozolone; tiomesterone; clostebol;mibolerone; nandrolone cyclotate; norbolethone; quinbolone; stenboloneacetate; tibolone; zeranol.

Analeptics:

modafinil; amineptine; endomide; etamivan; fenoxypropazine; fenozolone;hexapradol; nialamide; nicethamide.

Analgesics:

acetaminophen; alfentanil; aminobenzoate; aminobenzoate; anidoxime;anileridine; anileridine; anilopam; anirolac; antipyrine; aspirin;benoxaprofen; benzydamine; bicifadine hydrochloride; brifentanil; bromadoline; bromfenac; buprenorphine; butacetn; butixirate; butorphanol;butorphanol; carbamazepine; carbaspirin calcium; carbiphene;carfentanil; ciprefadol succinate; ciramadol; ciramadol; clonixeril;clonixin; codeine; codeine phosphate; codeine sulfate; conorphone;cyclazocine; dexoxadrol; dexpemedolac; dezocine; diflunisal;dihydrocodeine; dimefadane; dipyrone; doxpicomine; drinidene; enadoline;epirizole; ergo tamine tartrate; ethoxazene; etofenamate; eugenol;fenoprofen; fenoprofen calcium; fentanyl citrate; floctafenine;flufenisal; flunixin; flunixin meglumine; flupirtine; fluproquazone;fluradoline; flurbiprofen; hydr omorphone; ibufenac; indoprofen;ketazocine; ketorfanol; ketorolac; letimide; levomethadyl acetate;levomethadyl acetate hydrochloride; levonantradol; levorphanol;lofemizole; lofentanil oxalate; lorcinadol; lomoxicarn; magnesiumsalicylate; mefenamic add; menabitan; meperidine; meptazinol; methadone;methadyl acetate; methopholine; methotrimeprazine; metkephamid acetate;mimbane; mirfentanil; molinazone; morphine sulfate; moxazocine; nabitan;nalbuphine; nalmexone; namoxyrate; nantradol; naproxen; naproxen;naproxol; nefopam; nexeridine; noracymethadol; ocfentanil; octazamide;olvanil; oxetorone; oxycodone; oxycodone; oxycodone terephthalate;oxymorphone; pemedolac; pentamorphone; pentazocine; pentazocine;phenazopyridine; phenyramidol; picenadol; pinadoline; pirfenidone;piroxicam olamine; pravadoline; prodilidine; profadol; propiram;propoxyphene; propoxyphene napsilate; proxazole; proxorphan;pyrroliphene; remifentanil; salcolex; salethamide maleate; salicylamide;salicylate meglumine; salsalate; salicylate; spiradoline; sufentanil;sufentanil; talmetacin; talniflumate; talosalate; tazadolene;tebufelone; tetrydamine; tifurac; tilidine; tiopinac; tonazocine;tramadol; trefentanil; trolamine; veradoline; verilopam; volazocine;xorphanol; xylazine; zenazocine mesilate; zomepirac; sucapsaicin.

Androgens:

androstanolone; fluoxymesterone; mestanolone; mesterolone; metandienone;methyltestosterone; nandrolone decanoate; nandrolone phenpropionate;nisterime; oxandrolone; oxymesterone; oxymetholone; penmesterol;prasterone; silandrone; stanozolol; testosterone; testosteronecypionate; testosterone enanthate; testosterone ketolaurate;testosterone phenylacetate; testosterone propionate; trestolone.

Anesthetic Additives:

sodium oxibate.

Anesthetics (non-inhalation):

alfaxalone; amolanone; etoxadrol; fentanyl; ketamine; levoxadrol;methitural; methohexital; midazolam; minaxolone; propanidid; propoxate;pramoxine; propofol; remifentanyl; sufentanyl; tiletamine; zolamine.

Anesthetics (local):

ambucaine; amoxecaine; amylocaine; aptocaine; articaine; benoxinate;benzyl alcohol; benzocaine; betoxycaine; biphenamine; bucricaine;bumecaine; bupivacaine; butacaine; butamben; butanilicaine;carbizocaine; chloroprocaine clibucaine; clodacaine; cocaine;dexivacaine; diamocaine; dibucaine; dyclonine; elucaine; etidocaine;euprocin; fexicaine; fomocaine; heptacaine; hexylcaine; hydroxyprocaine;hydroxytetracaine; isobutamben; ketocaine; leucinocaine; lidocalne;mepivacaine; meprylcaine; octocalne; orthocaine; oxethacaine;oxybuprocaine; parabutoxycalne; phenacaine; pinolcaine; piperocaine;piridocaine; polidocanol; pramocaine; prilocaine; procaine;propanocaine; propipocaine; propoxycaine; proxymetacaine; pyrrocaine;quatacaine; quinisocaine; risocaine; rodocaine; ropivacaine; salicylalcohol; suicaine; tetracaine; trapencaine; trimecaine.

Appetite Suppressants:

amfepramone; amfetamine; aminorex; amfecloral; anisacril; benzfetamine;chlorphentermine; clobenzorex; cloforex; clominorex; clortermine;dexamfetamine; dexfenfluramine; difemetorex; efilamfetamine; etolorex;fenbutrazate; fencamfamln; fenfluramine; fenisorex; fenproporex;fludorex; fluminorex; formetorex; furfenorex; imanixil; indanorex;levamfetamine; levofacetoperane; levofenfluramine; levopropylhexedrine;mazindol; mefenorex; metamfepramone; morforex; norpseudoephedrine;orlistat; ortetamine; oxifentorex; pentorex; phendimetrazine;phenmetrazine; phentermine; picilorex; satietine; setazindol;sibutramine; triflorex; trifluorex.

Anthelmintics:

abamectin; albendazole; albendazole oxide; amidantel; amoscanate;antafenite; antazonite; anthelmycin; antholimine; bepheniumhydroxynaphthoate; bidimazium iodide; bisbendazole; bithionoloxide;bitoscanate; bromoxanide; brotianide; bunamidine; butamisole; butonate;cambendazole; carbantel; cidobendazole; clioxanide; closantel;dexamisole; diamfenetide; dichlorvos; diethylcarbamazine; dimantine;diphenan; doramectin; dribendazole; eprinomecUn; epsiprantel;etibendazole; febantel; fenbendazole; flubendazole; flurantel;ftalofyne; furodazole; haloxon; hexylresorcinol; imcarbofos; ivermectin;kainic acid; mebendazole; metrifonate; metyridine; morantel; moxidectin;naftalofos; netobimin; niclofolan; niclosamide; nitramisole; nitrodan;nitroscanate; nitroxinil; oltipraz; ontlanil, oxantel oxfendazole;oxibendazole; oxyclozanide; parbendazole; pexantel; piperamide;piperazine adipate; piperazine calcium edetate; piperamide praziquantel;proclonol; pyrantel pamoate; pyrantel tartrate; pyrvinium pamoate;rafoxanide; resorantel; salantel; spirazine; stilbanzium iodide;subendazole; tetramisole; thenium closilate; thiofuradene; tiabendazole;ticarbodine; tioxidazole; triclabendazole; triclofenol piperazine;uredofos; vincofos; zilantel.

Acne therapeutics:

adapalene; adelmidrol; benzoyl peroxide; betacarotene; cioteronel;delanterone; cyproterone; doretinel; erythromycin salnacedin;etretinate; fumaric acid; halofuginonen; inocoterone acetate;isotretinoin; linolenic acid; manoalide; masoprocol; mitotane;motretinide; namirotene; rosterelone; sumarotene; tazarotene;tematotene; tioxolone; topterone; tradecamide; tretinoin; triadimenol;zearalenone; zeranol; zimidoben.

Bronchodilators:

acefylline; azaspirium chloride; bambuterol; bamifylline; bitoiterol;broxaterol; butaprost; carbuterol; cipamfylline; colterol; doxaprost;doxofylline; dyphylline; enprofylline; ephedrine; eprozinol; etanterol;fenspiride; flutropium bromide; formoterol; guaithylline; hexoprenaline;Hoku-81; hoquizil; imoxiterol; ipragratine; ipratroplum bromide;isoetharine; isoproterenol; levosalbutamol; mabuterol; mequitamiumiodide; metaproterenol; mexafylline; nardeterol; nestifylline;nisbuterol; picumeterol; piquizil; pirbuterol; procaterol; reproterol;RO-24-4736; quazodine; quinterenol; racepinephrine; reproterol;rimiterol; salbutamol; salmeterol; saimeterol xinafoate; sevitropiummesilate; soterenol; sulfonterol; suloxifen; TA-2005; theophylline;terbutaline; theophylline ethylenediamine; tiaramide; tipetropiumbromide; tretoquinol; tulobuterol; zindotrine; zinterol.

Beta-blockers:

acebunolol; adaprolol; afurolol; alprenolol; alprenoxime; ancarolol;arnolol; arotinolol; atenolol; befunolol; benzodioxine; betaxolol;bevantolol; bisoprolol; bormetolol; bopindolol; bomaprolol; brefonalol;bucumolol; bufetolol; buftiralol; bunitrolol; bunolol; bupranolol;butaxamine; butidrine; burocrolol; butofilolol; carazolol; carteolol;carvedilol; celiprolol; cetamolol; cicloprolol; cinamolol; cloranolol;cyanopindolol; dalbraminol; dexpropranolol; diacetolol;dichlorisoproterenol; dilevalol; draquinolol; dropranolol; ecastolol;epanolol; ericolol; esatenolol; esmolol; exaprolol; falintolol;fiestolol; flusoxolol; hydroxycarteolol; hydroxytertatolol ; ICI-118551;idropranolol; indenolol; indopanolol; iprocrolol; isamoltan; labetalol;landiolol; levobetaxolol; levobunolol; levocicloprolol; levomoprolol;medroxalol; mephenoxalone; mepindolol; metalol; metipranolol;metoprolol; mindodilon; moprolol; nadolol; nadoxolol; nafetolol;napitane; nebivolol; neraminol; nifenalol; nipradilol; oberadilol;oxanamide; oxprenolol; pacrinolol; pafenolol; pamatolol; pargolol;parodilol; penbutolol; penirolol; PHQA-33; pindolol; pirepolol;practolol; prenalterol; primidolol; procinolol; pronetalol;propacetamol; propranolol; ractopamine; ridazolol; ronactolol;soquinolol; sotalol; TA-2005; talinolol; tazolol; teoprolol; tertatolol;terthianolol; tienoxolol; tilisolol; timolol; tiprenolol; tolamolol;toliprolol; tribendilol; trigevolol; xamoterol; xibenolol; Y-12541;ZAM1-1305.

Adrenergic Agonists:

betanidine; bretylium tosilate; cromanidine; debrisoquine; ethomoxane;guabenxan; guanabenz; guanacline; guanadrel; guanazodine; guancidine;guanclofine; guanethidine; guanfacine; guanisoquine; guanoclor;guanoctine; guanoxabenz; guanoxan; guanoxyfen; olmidine; piperoxan;pyroxamidine; solypertine; spirgetine.

Alpha 1 Antagonists:

abanoquil; adozelesin; alfuzosin; amosulalol; benoxathian; bunazosin;CI-926; DL017; dapiprazole; dihydroergotamine mesilate; doxazosin;euigenodilol; fenspiride; GI-231818; GYKI-12743; GYKI-16084; indoramine;metazosin; MK-912; monatepil; naftopidil; neldazosin; nesapidil;nicergoline; pelanserin; peradoxime; peraquinsine; peraUzole;perbufylline; phendioxan; phenoxybenzamine; phentolamine; podilfen;prazosin; quinazosin; RS-97078; proroxane; sertindole; SGB-1534;SL-89.0591; tamsulosin; tedisamil; terazosin; tibalosin; tiodazosin;tolazoline; trimazosin; upidosin; urapidil; yohimbine; zolertine.

ACE Inhibitors:

alacepril; benazepril; benazeprilat; BMS-189921; BRL-36378; captopril;ceronapril; CGS-13928C; cilazapril; cilazaprilat; dehydrocaptopril;delapril; enalapril; enalaprilat; EU4867; EXP-7711; fasidotril;fosinopril; fosinoprilat; idrapril; imidapril; imidaprilat; indolapril;libenzapril; lisinopril; mixanpril; moexipril; moexiprilat; moveltipril;omapatrilat; orbutopril; pentopril; perindopril; perindoprilat,pivopril; quinapril; quinaprilat; ramipril; rentiapril; sampatrilat;SCH-54470; spirapril; spiraprilat; temocapril; temocaprilat; teprotide;trandolapril; trandolaprilat; utibapril; utibaprilat; Z-13752A;zabicipril; zofenopril; zofenoprilat.

Renin Antagonists

CGP-38560; ciprokiren; CP-108671; enalkiren; ES-6864; FK-906; remikiren;terlakiren; zankiren.

Antiallergics such as PDE Inhibitors:

arofylline; atizoram, AWD-12-281(N-(3,5-dichloro-4-pyridinyl)-2-[1-(4-fluorobenzyl)-5-hydroxy-1H-in-dol-3-yl]-2-oxoacetamide);BAY-19-8004 (ethanesulfonic acid2-(2,4-dichlorophenylcarbonyl)-3-ureidobenzofuran-6-yl ester);benafentrine; CC-1088; CDC-801(β-[3-(cyclopentyloxy)4-methoxyphenyl]-1,3-dihydro-1,3-dioxo-2H-isoindole-2-propanamide);CDC-998; CI-1018; cilomilast(cis-[4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)cyclohexane-1-carboxylicacid); cilostazol; cipamfylline(8-amino-1,3-bis(cyclopropylmethyl)xanthine); D-4396; D-4418[N-(2,5-dichloro-3-pyridinyl)-8-methoxy-5-quinolinecarboxamide];darbufelone; denbufylline; ER-21355; filaminast; ibudilast; IC-485;indolidan; laprafylline; lixazinone; MESOPRAM[(−)-(R)-5-(4-methoxy-3-propoxyphenyl)-5-methyloxazolidin-2-one];nitraquazone; NM-702; olprinone; ORG-20241(4-(3,4-dimethoxyphenyl)-N2-hydroxythiazole-2-carboxamidine);piclamilast; pumafentrine((−)-cis-9-ethoxy-8-methoxy-2-methyl-1,2,3,4,4a,10Ob-hexahydro-6-(4-diisopropylaminocarbonylphenyl)benzo[c][1,6]-naphthyridine);quazinone; RO-15-2041; roflumilast(3-(cyclopropylmethoxy)-N-(3,5-dichloro-pyridyl)-4-(difluoromethoxy)-benzamide);rolipram; SCH-351591; SH-636; tibenelast(5,6-diethoxybenzo[b]thiophene-2-carboxylic acid); tolafentrine;trequinsin; V-11294A(3-[[3-(cyclopentyloxy)-4-methoxyphenyl]methyl]-N-ethyl-8-(1-methylethyl)-3H-purin-6-amine);YM-58997(4-(3-bromophenyl)-1-ethyl-7-methyl-1,8-naphthyridin-2(1H)-one); YM-976(4-(3-chlorophenyl)-1,7-diethylpyrido[2,3-d]pyrimidin-2(1H)-one);zardaverine.

Other Antiallergics for Asthma Treatment:

ablukast; atreleuton; bunaprolast; cinalukast; cromitrile; cromolyn;FPL-55712; iralukast; isamoxole; ketoufen; L-648051; levcromakalim;lodoxamide ethyl; lodoxamide tromethamine; montelukast; oxarbazole;piriprost; pirolate; pobilukast; pranlukast; ritolukast; sulukast;tiaramide; Ubenelast; tomelukast; verlukast; verofylline; zafirlukast;zileuton.

Other Antiallergics (for example leukotriene antagonists):

acitazanolast; acrivastine; alinastine; altoqualine; amlexanox;andolast; astemizole; ataquimast; azatadine; azelastine; bamipine;barmastine; batebulast; BAY-X-1005; BAY-X-7195; bepiastine; bepotastine;BIIL-284; bilastine; binizolast; buclizine; bunaprolast; cabastine;carebastine; cetirizine; CI-959; ciproxifan; clemastine; CMI-977;cromoglcic acid; cromolyn natrium; dametralast; desloratadine;dlmenhydrinate; diphenhydramine; doqualast; dorastine; E-4704;efietirizine; emedastine; enofelast; enoxamast; ebastine; eclazolast;epinastine; fexofenadine; flezelastine; HSR-609; KCA-757; levocabastine;levocetirizine; linetastine; loratadine; LY-293111; mapinastine;mequitamium iodide; mequitazin; minocromil, mizolastine; MK-886;moxastine; moxilubant; nedocromil; nedocromil calcium; nedocromilsodium; nivimedone; noberastine; norastemizole; octastine; ONO-4057;ontazolast; oxatomide; pemirolast; pentigetide; perastine; piclopastine;picumast; pirquinozol; poisonoak extract; probicromil; proxicromil;quazolast; quifenadine; quinotolast; raxofelast; repirinast; REV-5901-A;rocastine; rupatadine; SKF-S-106203; sequifenadine; setastine;sudexanox; tagorizine; talastine; tazanolast; tazifylline; temelastine;terfenadine; tetrazolast; texacromil; thiazinamium chloride; tiacrilast;tiprinast meglumine; tixanox; tranilast; WY-50295; ZD-3523; zepastine.

Amebicides:

1B-bisamidine; berythromycin; bialamicol; carbarsone; chloroquine;chloroquine; clamoxyquin; ciloquinol; dehydroemetine; difetarsone;diloxanide; emetine; etofamide; iodoquinol; lachnumon; liroldine;paromomycin sulfate; pinafide; quinfamide; satranidazole; stevaladil;stirimazole; symetine; teclozan; tetracycline; tilbroqulnol;

Antiandrogens:

abiraterone; benorterone; cioteronel; cyproterone; delanterone;delmadinone; drospirenone; epitiostanol; inocoterone; L-654066;minamestane; norgestimate; osaterone; oxendolone; progesterone;rosterelone; topterone; zanoterone.

Antianemics:

ancestim; diciferron; epoetin alfa; epoetin beta; epoetin epsilon;epoetin gamma; epoetin omega; ferrous sulfate, FK-352; folic acid;gleptoferron; glutathione monoisopropyl ester; leucovorin calcium;tucaresol; TYB-5220; velaresol;

Antianginals:

alinidine; amiodarone; amlodipine besylate; amlodipine maleate;azaclorzine; bamidipine; bertosamil; betaxolol; bertosamil; bevantolol;bimakalim; butoprozine; carvedilol; CD832; CERM-11956; cinepazetmaleate; crobenetine; cyclovirubuxine-D; desocriptine; diproteverine;dopropidil; elgodipine; EMD-57283; eniporide; ethacizine; fantofarone;FK-409; flestolol; flosaudil; flosequinan; FR-46171; GP-1-468; GP-1-531;hyperin; ipramidil; isosorbide dinitrate; ivabradine; KC-764; KRN-2391;KW-3635; ligustizine; linsidomine; metoprolol succinate; mibefradil;mildronate; mivazerol; molsidomine; monatepil maleate; nafagrel; NK-341;OP-2000; pirsidomine; pivazide; pranidipine; primidolol; ranolazine;SL-87.0495; ST-1324; tedisamil; tosifen; vatanidipine; verapamil;Y-27152; zatebradine.

Anxiolytics:

adatanserin; alpidem; binospirone mesilate; bretazenil; glemanserin;ipsapirone; mirisetron maleate; ocinaplon; ondansetron; panadiplon;pancopride; pazinaclone; serazapine; tandospirone citrate; zalospirone.

Antiarthritics:

AI-200; auranofin; aurothioglucose; cipemastat; etanercept; etebenecid;interleukin-6; leflunomide; lenercept; lobenzarit; lodelaben: M-5010;parecoxib; rofecoxib; RS-130830; S-2474; TSA-234; valdecoxib;

Antiatherosclerotics:

H-327/86; mifobate; lodazecar; riboflavin butyrate; timefurone.

Bacteriostatics:

acedapsone; acetosulfone sodium; alamecin; alexidine; amdinocillin;amdlnocillin pivoxil; amicycline; amifloxacin; amifloxacin mesilate;amikacin; amikacin sulfate; aminosalicyllc acid; aminosalicylate sodium;amoxicillin; amphomycin; ampicillin; ampicillin sodium; apaicillinsodium; apramycin; aspartocin; astromicin sulfate; avilamycin;avoparcin; azithromycin; aziocillin; aziocillin sodium; bacampicillinhydrochloride; bacitracin; bacitracin methylene disalicylate; bacitracinzinc; bambermycins; benzoylpas calcium; berythromycin; betamicinsulfate; biapenem; biniramycin; biphenamine hydrochloride; bispyrithionemagsulfex; butikacin; butirosin sulfate; capreomycin sulfate; carbadox;carbenicillin disodium; carbenicillin indanyl sodium; carbenicillinphenyl sodium; carbenicillin; carumonam sodium; cefaclor; cefadroxil;cefamandole; cefamandole nafate; cefamandole sodium; cefaparole;cefatrizine; cefazaflur sodium; cefazolin; cefazolin sodium;cefbuperazone; cefdinir; cefepime; cefepime; cefetecol; cefixime;cefmenoxime; cefmetazole; cefmetazole sodium; cefonicid monosodium;cefonicid sodium; cefoperazone sodium; ceforanide; cefotaxime sodium;cefotetan; cefotetan disodium; cefotiam; cefoxitin; cefoxitin sodium;cefpimizole; cefpimizole sodium; cefpiramide; cefpiramide sodium;cefpirome sulfate; cefpodoxime proxetil; cefprozil; cefroxadine;cefsulodin sodium; ceftazidime; ceftibuten; ceftizoxime sodium;ceftriaxone sodium; cefuroxime; cefuroxime axetil; cefuroxime pivoxetil;cefuroxime sodium; cephacetrile sodium; cephalexin; cephalexin;cephaloglycin; cephaloridine; cephalothin sodium; cephapirin sodium;cephradine; cetocycline; cetophenicol; chloramphenicol; chloramphenicolpalmitate; chloramphenicol pantothenate complex; chloramphenicol sodiumsuccinate; chlorhexidine phosphanilate; chloroxylenol; chlortetracyclinebisulfate; chlortetracycline; cinoxacin; ciprofloxacin; ciprofloxacin;cirolemycin; clarithromycin; clinafloxacin; clindamycin; clindamycin;clindamycin palmitate; clindamycin phosphate; clofazimine; cloxacillinbenzathine; cloxacillin sodium; cloxyquin; colistimethate sodium;colistin sulfate; coumermycin; coumermycin sodium; cyclacillin;cycloserine; dalfopristin; dapsone; daptomycin; demeclocycline;demeclocycline; demecycline; denofungin; diaveridine; dicloxacillin;dicloxacillin sodium; dihydrostreptomycin sulfate; dipyrithione;dirithromycin; doxycycline; doxycycline calcium; doxycycline fosfatex;doxycydine hyclate; droxacin sodium; enoxacin; epicillin;epitetracycline; erythromycin; erythromycin acistrate; erythromycinestolate; erythromycin ethylsuccinate; erythromycin gluceptate;erythromycin lactoblonate; erythromycin propionate; erythromycinstearate; ethambutol; ethionamide; fleroxacin; floxacillin; fludalanine;flumequine; fosfomycin; fosfomycin tromethamine; fumoxicillin;furazolium chloride; furazolium tartrate; fusidate sodium; fusidic acid;gentamicin sulfate; gloximonam; gramicidin; haloprogin; hetacillin;hetacillin; hexedine; ibafloxacin; imipenem; isoconazole; isepamicin;isoniazid; josamycin; kanamycin sulfate; kitasamycin; levofuraltadone;levopropylcillin; lexithromycin; lincomycin; lincomycin; lomefloxacin;lomefloxacin; lomefloxacin mesilate; loracarbef; mafenide; meclocycline;meclocycline sulfosalicylate; megalomicin phosphate; mequidox;meropenem; methacycline; methacycline; methenamine; methenaminehippurate; methenamine mandelate; methicillin sodium; metioprim;metronidazole; metronidazole phosphate; meziocillin; meziocillin sodium;minocycline; minocycline; mirincamycin; monensin; monensin sodium;nafcilin sodium; nalidixate sodium; nalidixic acid; natainycin;nebramycin; neomycin palmitate; neomycin sulfate; neomycin undecylenate;netilmicin sulfate; neutramycin; nifuiradene; nifuraldezone; nifuratel;nifuratrone; nifurdazil; niftrimide; niflupirinol; nifurquinazol;nifurthiazole; nitrocycline; nitrofurantoin; nitromlde; norfloxacin;novobiocin sodium; ofloxacin; onnetoprim; oxacillin sodium; oximonam;oximonam sodium; oxolinic acid; oxytetracycline; oxytetracyclinecalcium; oxytetracycline; paldimycin; parachlorophenol; paulomycin;pefloxacin; pefloxacin mesilate; penamecillin; penicillin G benzathine;penicillin G; penicillin G procaine; penicillin G sodium; penicillin V;penicillin V benzathine; penicillin V hydrabamine; penicillin V;pentizidone sodium; phenyl aminosalicylate; piperacillin sodium;pirbenicillin sodium; piridicillin sodium; pirlimycin; pivampicillin;pivampicillin pamoate; pivampicillin probenate; polymyxin B sulfate;porfiromycin; propikacin; pyrazinamide; pyrithione zinc; quindecamineacetate; quinupristin; racephenicol; ramoplanin; ranimycin; relomycin;repromicin; rifabutin; rifametane; rifamexil; rifamide; rifampin;rifapentine; rifaximin; rolitetracycline; rolitetracycline nitrate;rosaramicin; rosaramicin butyrate; rosaramicin propionate; rosaramicinsodium phosphate; rosaramicin stearate; rosoxacin; roxarsone;roxithromycin; sancycline; sanfetrinem sodium; sarmoxicillin;sarpicillin; scopafungin; sisomicin; sisomicin sulfate; sparfloxacin;spectinomycin; spiramycin; stallimycin; steffimycin; streptomycinsulfate; streptonicozid; sulfabenz; sulfabenzamide; sulfacetamide;sulfacetamide sodium; sulfacytine; sulfadiazine; sulfadiazine sodium;sulfadoxine; sulfalene; sulfamerazine; sulfameter; sulfamethazine;sulfamethizole; sulfamethoxazole; sulfamonomethoxine; sulfamoxole;sulfanilate zinc; sulfanitran; sulfasalazine; sulfasomizole;sulfathiazole; sulfazamet; sulfisoxazole; sulfisoxazole acetyl;sulfisboxazole diolamine; sulfomyxin; sulopenem; sultarmicillin;suncillin sodium; talampicillin; telcoplanin; temafloxacin; temocillin;tetracycline; tetracycline; tetracycline phosphate complex; tetroxoprim;thiamphenicol; thiphencillin; ticarcillin cresyl sodium; ticarcillindisodium; ticarcillin monosodium; ticlatone; tiodonium chloride;tobramycin; tobramycin sulfate; tosufloxacin; trimethoprim; trimethoprimsulfate; trisulfapyrimidines; troleandomycin; trospectomycin sulfate;tyrothricin; vancomycin; vancomycin; virginiamycin; zorbamycin.

Anticholinergics:

alverine citrate; anisotropine methylbromide; atropine; atropine oxide;atropine sulfate; belladonna; benapryzine; benzetimide; benziloniumbromide; biperiden; biperiden; biperiden lactate; clidinium bromide;cyclopentolate; dexetimide; dicyclomine; dihexyverine; domazolinefumarate; elantrine; elucaine; ethybenztropine; eucatropine;glycopyrrolate; heteronium bromide; homatropine hydrobromide;homatropine methylbromide; hyoscyamine; hyoscyamine hydrobromide;hyoscyamine sulfate; isopropamide iodide; mepenzolate bromide;methylatropine nitrate; metoquizine; oxybutynin chloride; parapenzolatebromide; pentapiperium methylsulfate; phencarbamide; poldinemethylsulfate; proglumide; propantheline bromide; propenzolate;scopolamine hydrobromide; tematroplum methylsulfate; tiquinamide;tofenacin; toquizine; triampyzine sulfate; trihexyphenidyl; tropicamide.

Anticoagulants:

ancrod; ardeparin sodium; bivalirudin; bromindione; dalteparin sodium;desirudin; dicumnarol; heparin calcium; heparin sodium; lyapolatesodium; nafamostat mesilate; phenprocoumon; tinzaparin sodium; warfarinsodium.

Anticonvulsants:

albutoin; ameltolide; atolide; buramate; carbamazepine; cinromide;citenamide; clonazepam; cyheptamide; dezinamide; dimethadione;divalproex sodium; eterobarb; ethosuximide; ethotoin; flurazepam;fluzinamide; fosphenytoin sodium; gabapentin; ilepcimide; lamotrigine;magnesium sulfate; mephenytoin; mephobarbital; methetoin; methsuximide;milacemide; nabazenil; nafimidone; nitrazepam; phenacemide;phenobarbital; phenobarbital sodium; phensuximide; phenytoin; phenytoinsodium; primidone; progabide; ralitoline; remacemide; ropizine;sabeluzole; stiripentol; sulthiame; thiopental sodium; tiletamine;topiramate; trimethadione; valproate sodium; valproic acid; vigabatrin;zoniclezole; zonisamide.

Antidepressants:

adatanserin; adinazolam; adinazolam mesilate; alaproclate; aletamine;amedalin; amitriptyline; amoxapine; aptazapine maleate; azaloxanfumarate; azepindole; azipramine; bipenamol; bupropion; butacetin;butriptyline; caroxazone; cartazolate; ciclazindol; cidoxepin;cilobamine mesilate; clodazon; clomipramine; cotinine fumarate;cyclindole; cypenamine; cyprolidol; cyproximide; daledalin tosylate;dapoxetine; dazadrol maleate; dazepinil; desipramine; dexamisole;deximafen; dibenzepin; dioxadrol; dothiepin; doxepin; duloxetine;eclanamine maleate; encyprate; etoperidone; fantridone; fehmetozole;fenmetramide; fezolamine fumarate; fluotracen; fluoxetine; fluoxetine;fluparoxan; gamfexine; guanoxyfen sulfate; imafen; imiloxan; imipramine;indeloxazine; intriptyline; lprindole; isocarboxazid; ketipraminefumarate; lofepramine; lortalamine; maprotiline; maprotiline;melitracen; milacemide; minaprine; mirtazapine; moclobemide; modalinesulfate; napactadine; napamezole; nefazodone; nisoxetine; nitrafudam;nomifensine maleate; nortriptyline; octriptyline phosphate; opipramol;oxaprotiline; oxypertine; paroxetine; pheneizine sulfate; pirandamine;pizotyline; pridefine; prolintane; protriptyline; quipazine maleate;rolicyprine; seproxetine; sertraline; sibutramine; sulpiride;suritozole; tametraline; tampramine fumarate; tandamine; thiazesim;thozalinone; tomoxetine; trazodone; trebenzomine; trimipramine;trimipramine maleate; venlafaxine; viloxazine; zimeldine; zometapine.

Antidiabetics:

acetohexamide; bimoclomol; BM-17.0249; buformin; butoxamine;carbutamide; centpiperalone; chlorpropamide; clomoxir; etoformin;etomoxir; fenbutamide; GI-262570; gliamilide; glibenclamide;glibornuride; glibutimine; glicaramide; glicetanile sodium; gliclazide;glicondamide; glidazamide; gliflumide; glimepiride; glipalamide;glipizide; gliquidone; glisamuride; glisentide; glisindamide;glisolamide; glisoxepide; glucagon; glyburide; glybuthiazol; glybuzole;glyclopyramide; glycyclamide; glyhexamide; glymidine sodium;glyoctamide; glyparamide; glypinamide; glyprothiazol; glysobuzole;heptolamide; HMR-1964; insulin; insulin argine; insulin aspart; insulindalanat; insulin defalan; insulin detemir; insulin glargine; insulinhuman; insulin human, isophane; insulin human zinc; insulin human zinc,extended; insulin, isophane; insulin lispro; insulin, neutral; insulinzinc; insulin zinc, extended; insulin zinc; isaglidole; JTT-501;JTT-608; mebenformin; metahexamide; metfomin; methyl palmoxirate;metyrapone; midaglizole; mitiglinide; nateglinide; NN-304; NVP-DPP-728;palmoxirate sodium; PNU-106817; pramlintide; proinsulin human; seglitideacetate; tibeglisene; tiformin; tolazamide; tolbutamide; tolpyrramide;

Aldose Reductase Inhibitors:

AD-5467; alrestatin; ciglitazone; darglitazone; englitazone sodium;epalrestat; fidarestat; imirestat; linogliride; linogliride; MCC-555;minalrestat; NZ-314; pioglitazone; pirogliride; ponalrestat; sorbinil;risarestat; rosiglitazone; tendamistat, tolrestat; troglitazone;zenarestat; zopolrestat.

Alpha-glucosidase Inhibitors:

acarbose; camiglibose; emiglitate; englitazone; miglitol; moranoline;voglibose.

Antidiarrheals:

rolgamidine, diphenoxylate (Lomotil), metronidazole (Flagyl),methylprednisolone (Medrol), sulfasalazine (Azulfidine).

Antidiuretics:

argipressin tannate; desmopressin acetate; lypressin.

Antidotes:

dimercaprol; edrophonium chloride; fomepizole; leucovorin calcium;levoleucovorin calcium; methylene blue; protamine sulfate.

Antiemetics:

alosetron; batanopride; bemesetron; benzquinamide; chlorpromazine;chlorpromazine; clebopride; cyclizine; dimenhydrinate; diphenidol;diphenidol; diphenidol pamoate; dolasetron mesilate; domperidone;dronabinol; fludorex; flumeridone; galdansetron; granisetron;granisetron; lurosetron mesilate; meclizine; metoclopramide;metopimazine; ondansetron; pancopride; prochlorperazine;prochlorperazine edisylate; prochlorperazine maleate; promethazine;thiethylperazine; thiethylperazine malate; thiethylperazine maleate;trimethobenzamide; zacopride.

Antiepileptics:

felbamate; loreclezole; tolgabide.

Antiestrogens (non-steroidal):

clometherone; delmadinone acetate; nafoxidine; nitromifene citrate;raloxifene; tamoxifen citrate; toremifene citrate; trioxifene mesilate.

Antifibrinolytics:

camostat; nafamostat mesilate.

Fungistatics:

acrisorcin; ambruticin; amphotericin B; azaconazole; azaserine;basifungin; bifonazole; biphenamine; bispyrithione magsulfex;butoconazole nitrate; calcium undecylenate; candicidin; carbol-fuchsin;chlordantoin; ciclopirox; ciclopirox olamine; cilofungin; cisconazole;clotrimazole; cuprimyxin; denofungin; dipyrithione; doconazole;econazole; econazole nitrate; enilconazole; ethonam nitrate;fenticonazole nitrate; filipin; fluconazole; flucytosine; fungimycin;griseofulvin; hamycin; isoconazole; itraconazole; kalafungin;ketoconazole; lomofimgin; lydimycin; mepartricin; miconazole; miconazolenitrate; monensin; monensin sodium; naftifine; neomycin undecylenate;nifuratel; nifurmerone; nitralamine; nystatin; octanoic acid; orconazolenitrate; oxiconazole nitrate; oxifungin; parconazole; partricin; iodide;proclonol; pyrithione zinc; pyrrolnitrin; rutamycin; sanguinariumchloride; saperconazole; scopafungin; selenium sulfide; sinefungin;sulconazole nitrate; terbinafine; terconazole; thiram; ticlatone;tioconazole; tolciclate; tolindate; tolnaftate; triacetin; triafungin;undecylenic acid; viridofulvin; zinc undecylenate; zinoconazole.

Glaucoma Drugs:

alprenoxime; colforsin; dapiprazole; dipivefrin; naboctate; pilocarpine;pimabine.

Antihistamines:

acrivastine; antazoline phosphate; astemizole; azatadine maleate;barmastine; bromodiphenhydramine; brompheniramnine maleate;carbinoxamine maleate; cebrizine; chlorpheniramine maleate;chlorpheniramine polistirex; cinnarizine; clemastine; clemastinefumarate; closiramine aceturate; cycliramine maleate; cyclizine;cyproheptadine; dexbrompheniramnine maleate; dexchlorpheniraminemaleate; dimethindene maleate; diphenhydramine citrate;diphenhydramnine; dorastine; doxylamine succinate; ebastine;levocabastine; loratadine; mianserin; noberastine; orphenadrine citrate;pyrabrom; pyrilamine maleate; pyroxamnine maleate; rocastine;rotoxamine; tazifylline; temelastine; terfenadine; tripelennaminecitrate; tripelennamine; triprolidine; zolamine.

Lipid-lowering Agents:

cholestyramine resin; clofibrate; colestipol; crilvastatin; dalvastatin;dextrothyroxine sodium; fluvastatin sodium; gemfibrozil; lecimibide;lovastatin; niacin; pravastatin sodium; probucol; simvastatin;tiqueside; xenbucin; acifran; beloxamide; bezafibrate; boxidine;butoxamine; cetaben sodium; ciprofibrate; gemcadiol; halofenate;ifibrate; meglutol; nafenopin; pimetine; theofibrate; tibric acid;treloxinate.

Antihypertensives:

alfuzosin; alipamide; althiazide; amiquinsin; amlodipine besylate;amlodipine maleate; anaritide acetate; atiprosin maleate; belfosdil;bemitradine; bendacalol mesilate; bendroflumethiazide; benzthiazide;betaxolol; bethanidine sulfate; bevantolol; biclodil; bisoprolol;bisoprolol fumarate; bucindolol; bupicomide; buthiazide: candoxatril;candoxatrilat; captopril; carvedilol; ceronapril; chlorothiazide sodium;cicletanine; cilazapril; clonidine; clonidine; clopamide;cyclopenthiazide; cyclothiazide; darodipine; debrisoquin sulfate;delapril; diapamide; diazoxide; dilevalol; diltiazem malate; ditekiren;doxazosin mesilate; ecadotril; enalapril maleate; enalaprilat;enalkiren; endralazine mesilate; epithiazide; eprosartan; eprosartanmesilate; fenoldopam mesilate; flavodilol maleate; flordipine;flosequinan; fosinopril sodium; fosinoprilat; guanabenz; guanabenzacetate; guanacline sulfate; guanadrel sulfate; guancydine; guanethidinemonosulfate; guanethidine sulfate; guanfacine; guanisoquin sulfate;guanoclor sulfate; guanoctine; guanoxabenz; guanoxan sulfate; guanoxyfensulfate; hydralazine; hydralazine polistirex; hydroflumethiazide;indacrinone; indapamide; indolaprif; indoramin; indoramin; indorenate;lacidipine; leniquinsin; levcromakalim; lisinopril; lofexidine;losartan; losulazine; mebutamate; mecamylamine; medroxalol; medroxalol;methalthiazide; methyclothiazide; methyldopa; methyidopate;metipranolol; metolazone; metoprolol fumarate; metoprolol succinate;metyrosine; minoxidil; monatepil maleate; muzolimine; nebivolol;nitrendipine; oformine; pargyline; pazoxide; pelanserin; perindoprilerbumine; phenoxybenzamine; pinacidil; pivopril; polythiazide; prazosin;primidolol; prizidilol; quinapril; quinaprilat; quinazosin; quinelorane;quinpirole; quinuclium bromide; ramipril; rauwolfia serpentina;reserpine; saprisartan; saralasin acetate; sodium nitroprusside;sulfinalol; tasosartan; teludipine; temocapril; terazosin; terlakiren;tiamenidine; tiamenidine; ticrynafen; Unabinol; tiodazosin; tipentosin;trichlormethiazide; trimazosin; trimethaphan camsylate; trimoxamine;tripamide; xipamide; zankiren; zofenoprilat arginine.

Antihypotensives:

ciclafrine; midodrine.

Antiinflammatory Agents:

alclofenac; alclometasone dipropionate; algestone acetonide; alphaamylase; amcinafal; amcinafide; amfenac sodium; amiprilose; anakinra;anirolac; anitrazafen; apazone; balsalazide disodium; bendazac;benoxaprofen; benzydamine; bromelains; broperamole; budesonide;carprofen; cicloprofen; cintazone; cliprofen; clobetasol propionate;clobetasone butyrate; clopirac; cloticasone proplonate; cormethasoneacetate; cortodoxone; deflazacort; desonide; desoximetasone;dexamethasone dipropionate; diclofenac; diclofenac sodium; diflorasonediacetate; diflumidone sodium; diflunisal; difluprednate; diftalone;dimethyl sulfoxide; drocinonide; endrysone; enlimomab; enolicam sodium;epirizole; etodolac; etofenamate; felbinac; fenamole; fenbufen;fenclofenac; fenclorac; fendosal; fenpipalone; fentiazac; flazalone;fluazacort; flufenamic acid; flumizole; flunisolide acetate; flunixin;flunixin meglumine; fluocortin butyl; fluorometholone acetate;fluquazone; flurbiprofen; fluretofen; fluticasone propionate;furaprofen; furobufen; halcinonide; halobetasol propionate; halopredoneacetate; ibufenac; ibuprofen; ibuprofen aluminum; ibuprofen piconol;ilonidap; indomethacin; indomethacin sodium; indoprofen; indoxole;intrazole; isoflupredone acetate; isoxepac; isoxicam; ketoprofen;lofemizole; lomoxicam; lonazolac; loteprednol etabonate; meclofenamatesodium; meclofenamic acid; meclorisone dibutyrate; mefenamic acid;mesalamine; meseclazone; methylprednisolone suleptanate; momiflumate;nabumetone; naproxen; naproxen sodium; naproxol; nimazone; olsalazinesodium; orgotein; orpanoxin; oxaprozin; oxyphenbutazone; paranyline;pentosan polysulfate sodium; phenbutazone sodium glycerate; pirfenidone;piroxicam; piroxicam cinnamate; piroxicam olamine; pirprofen;prednazate; prifelone; prodolic acid; proquazone; proxazole; proxazolecitrate; rimexolone; romazarit; salcolex; salnacedin; salsalate;sanguinarium chloride; seclazone; sermetacin; sudoxicam; sulindac;suprofen; talmetacin; talniflumate; talosalate; tebufelone; tenidap;tenidap sodium; tenoxicam; tesicam; tesimide; tetrydamine; tiopinac;tixocortol pivalate; tolmetin; tolmetin sodium; triclonide;triflumidate; zidometacin; zomepirac sodium.

Antimalarials:

acedapsone; amodiaquine; amquinate; arteflene; chloroquine; chloroquine;chloroquine phosphate; cycloguanil pamoate; enpiroline phosphate;halofantrine; hydroxychloroquine sulfate; mefloquine; menoctone;mirincamycin; primaquine phosphate; pyrimethamine; quinine sulfate;tebuquine.

Microbicides:

aztreonam; chlorhexidine gluconate; imidurea; lycetamine; nibroxane;pirazmonam sodium; propionic acid; pyrithione sodium; sanguinariumchloride; tigemonam dicholine.

Antimigraine Agents:

almotriptan; alniditan; avitriptan; azasetron; azatadine; bemesetron;BIBN4096BS; BMS-181885; bromocriptine; dolasetron; donitriptan;ebalzotan; eletriptan; ergotamine; frovatriptan; iprazochrome; IS-159;lisuride; lomerizine; LY-334370; LY-53857; metergoline; metergotamine;methysergide; naratriptan; ORG-GC94; oxetorone; pipethiadene; pizotifen;propisergide; rizatriptan; sergolexole; sumatriptan; tropanserin;tropoxin; UK-116044; valofane; zatosetron; zolmitriptan.

Active Ingredients for Sea Sickness and Vomiting:

buclizine; cyclizine lactate; naboctate.

Cytostatics:

acivicin; aclarubicin; acodazole; acronine; adozelesin; aldesleukin;altretamine; ambomycin; ametantrone acetate; aminoglutethimide;amsacrine; anastrozole; anthramycin; asparaginase; asperlin;azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide;bisantrene; bisnafide dimesilate; bizelesin; bleomycin sulfate;brequinar sodium; bropirimine; busulfan; cactinomycin; calusterone;caracemide; carbetimer; carboplatin; carmustine; carubicin; carzelesin;cedefingol; chlorambucil; cirolemycin; cisplatin; cladribine; crisnatolmesilate; cyclophosphamide; cytarabine; dacarbazine; dactinomycin;daunorubicin; decitabine; dexormaplatin; dezaguanine; dezaguaninemesilate; diaziquone; docetaxel; doxorubicin; doxonubicin; droloxifene;droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate;eflomithine; elsamitrucin; enloplatin; enpromate; epipropidine;epirubicin; erbulozole; esorubicin; estramustine; estramustine phosphatesodium; etanidazole; ethiodized oil I 131; etoposide; etoposidephosphate; etoprine; fadrozole; fazarabine; fenretinide; floxuridine;fludarabine phosphate; fluorouracil; flurocitabine; fosquidone;fostriecin sodium; gemcitabine; gemcitabine; gold Au 198; hydroxyurea;idarubicin; ifosfamide; ilmofosine; interferon alfa-2a; interferonalfa-2b; interferon alfa-n1; interferon alfa-n3; interferon beta-I a;interferon gamma-I b; Iproplatin; irinotecan; lanreotide acetate;letrozole; leuprolide acetate; liarozole; lometrexol sodium; lomustine;losoxantrone; masoprocol; maytansine; mechlorethamine; megestrolacetate; melengestrol acetate; melphalan; menogaril; mercaptopurine;methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide;mitocarcin; mitocromin; mitogillin; mitomalcin; mitomycin; mitosper;mitotane; mitoxantrone; mycophenolic acid; nocodazole; nogalamycin;ormaplatin; oxisuran; paclitaxel; pegaspargase; peliomycin;pentamustine; peplomycin sulfate; perfosfamide; pipobroman; piposulfan;piroxantrone; plicamycin; plomestane; porfimer sodium; porfiromycin;prednimustine; procarbazine; puromycin; puromycin; pyrazofurin;riboprine; rogletimide; safmgol; safingol; semustine; simtrazene;sparfosate sodium; sparsomycin; spirogermanium; spiromustine;spiroplatin; streptonigrin; streptozocin; strontium chloride Sr 89;sulofenur; talisomycin; taxane; taxold; tecogalan sodium; tegafur;teloxantrone; temoporfin; teniposide; teroxirone; testolactone;thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; topotecan;toremifene citrate; trestolone acetate; triciribine phosphate;trimetrexate; trimetrexate glucuronate; triptorelin; tubulozole; uracilmustard; uredepa; vapreotide; verteporfin; vinblastine sulfate;vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate;vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate;vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin;zinostatin; zorubicin.

Active Ingredient for Combination Therapy with Cytostatics:

imipramine and desipramine.

Antiparkinson Agents:

benztropine mesilate; biperiden; biperiden; biperiden lactate;carmantadine; ciladopa; dopamantine; ethopropazine; lazabemide;levodopa; lometraline; mofegiline; naxagolide; pareptide sulfate;procyclidine; quinetorane; ropinirole; selegiline; tolcapone;trihexyphenidyl; antiperistaltic; difenoximide; difenoxin;diphenoxylate; fluperamide; lidamidine; loperamide; malethamer;nufenoxole; paregoric.

Antiproliferative Active Ingredients:

piritrexim isethionate.

Antiprotozoal Active Ingredients:

amodiaquine; azanidazole; bamnidazole; carnidazole; chlortetracyclinebisulfate; chlortetracycline; flubendazole; flunidazole; halofuginonehydrobromide; imidocarb; ipronidazole; metronidazole; misonidazole;moxnidazole; nitarsone; partricin; puromycin; puromycin; ronidazole;sulnidazole; tinidazole.

Active Ingredients for Treating Pruritus:

cyproheptadine; methdilazine; methdilazine; trimeprazine tartrate.

Psoriasis Active Ingredients:

acitretin; anthralin; azaribine; calcipotriene; cycloheximide; enazadremphosphate; etretinate; liarozole fumarate; lonapalene; tepoxalin.

Neuroleptics:

acetophenazine maleate; alentemol hydrobromide; alpertine; azaperone;batelaplne maleate; benperidol; benzindopyrlne; brofbxine; bromperidol;bromperidol decanoate; butaclamol; butaperazine; butaperazine maleate;carphenazine inaleate; carvotroline; chlorpromazine; chlorpromazine;chlorprothixene; cinperene; cintriamide; comacran phosphate;clopenthixol; clopimozide; clopipazan mesilate; cloroperone;clothlapine; clothixamide maleate; clozapine; cyclophenazine;droperidol; etazolate; fenimide; flucindole; flumezapine; fluphenazinedecanoate; fluphenazine enanthate; fluphenazine; fluspiperone;fluspirilene; flutroline; gevotroline; halopemide; haloperidol;haloperidol decanoate; iloperidone; imidoline; lenperone; mazapertinesuccinate; mesoridazine; mesoridazine besylate; metiapine; milenperone;milipertine; molindone; naranol; neflumozide; ocaperidone; olanzapine;oxiperomide; penfluridol; pentiapine maleate; perphenazine; pimozide;pinoxepin; pipamperone; piperacetazine; pipotiazine painlitate;piquindone; prochlorperazine edisylate; prochlorperazine maleate;promazine; remoxipride; remoxipride; rimcazole; seperidol; sertindole;setoperone; spiperone; thioridazine; thioridazine; thiothixene;thiothixene; tioperidone; tiospirone; trifluoperazine; trifluperidol;triflupromazine; triflupromazine; ziprasidone.

Antirheumatics:

auranofin; aurothioglucose; bindarit; lobenzarit sodium; phenylbutazone;pirazolac; prinomide tromethamine; seprilose.

Antischistosomal Agents:

becanthone; hycanthone; lucanthone; niridazole; oxamniquine;pararosaniline pamoate; teroxalene.

Active Ingredients for Treating Seborrhea:

chloroxine; piroctone; piroctone olamine; resorcinol monoacetate.

Antispasmolytics:

stilonium iodide; tizanidine.

Antithrombotics:

argatroban; anagrelide; bivalirudin; dalteparin sodium; domitroban;daltroban; danaparoid sodium; dazoxiben; E-3040; efegatran sulfate;enoxaparin sodium; ifetroban; ifetroban sodium; KW-3635; LCB-2853;linotroban; mipitroban; NM-702; picotamide; ramatroban; ridogrel;S-1452; samixogrel; seratrodast; sulotroban; terbogrel; Unzaparinsodium; trifenagrel.

Antitussives:

benproperine; benzonatate; bibenzonium bromide; bromhexine; butamiratecitrate; butetamate; ciobutinol; chlofedanol; codeine; codeinepolistirex; codoxime; dextromethorphan; dextromethorphan polistirex;dihydrocodeine; dimethoxanate; dropropizine; drotebanol; eprazinone;ethyl dibunate; fedrilate; gualapate; hydrocodone; hydrocodonepolistirex; iquindamine; isoaminile; levdropropizine; levopropoxyphenenapsylate; medazomide; meprotixol; moguisteine; morclofone; nepinalone;noscapine; pemerid nitrate; pentoxyverine; pholcodine; picoperine;pipazetate; prenoxdiazine; promolate; saredutant; sodium dibunate;suxemerid sulfate; thebacon; tipepidine; vadocaine; zipeprol.

Antiulcer Aents:

histamine H2 antagonists

BL-6271; BL-6341A; BMY-25368; BRL-28390; cimetidine; dalcotidine;donetidine; ebrotidine; etintidine; famotidine; ICI-162846; icotidine;IGN-2098; isotiquimide; lafutidine; lamtidine; lavoltidine; lupitidine;mifentidine; niperotidine; nizatidine; osutidine; oxmetidine; pibubdine;pifatidine; ramixotidine; ranitidine; ranitidine bismuth citrate;ranitidine nitrate; roxatidine; sufotidine; TAS; tiotidine; venritidine;WHR-2348; YM-14471; zaltidine; zolantidine.

Proton Pump Inhibitors

disuprazole; esomeprazole; FPL-65372-XX; H-335/25; H-405/02; HN-11203;IY-81149; lansoprazole; leminoprazole; lucartamide; N-2220; NC-1300;nepaprazole; omeprazole; pantoprazole; pantoprazole sodium; picartamide;picoprazole; pumaprazole; rabeprazole; saviprazole; SCH-28080;SKF-95-601; SKF-96067; SKF-97574; T-330; T-776; tenatoprazole;ufiprazole; YH-1885; YM-19020.

Prostaglandins

arbaprostil; butaprost; deprostil; dimethyidinoprostone; dimoxaprost;enisoprost; enprostil; mexiprostil; misoprostol; nocloprost;ornoprostil; oxoprostol; remiprostol; rioprostil; rosaprostol; SC-30249;spiriprostli; TEI-1226; tiprostanide; trimoprostil;

Other Antiulcer Agents

aceglutamide aluminium; AD-1308; benexate; benzotript; beperidiumiodide; bifemelane; BTM-1086; cadexomer iodine; cetraxate; CF-19415;CHINOIN-127; darenzepine; deboxamet; detralfate; DH-6615; dosmalfate;ecabapide; ecabet; esaprazole; espatropate; gefamate; irsogladine;KW-5805; lactalfate; lozilurea; MAR-99; MCI-727; MDL-201034; mezolidon;molfamate; nolinium bromide; nuvenzepine; octreotide; P-1100; pifamine;pirenzepine; plaunotol; polaprezinc; rebamipide; RGH-2961; rispenzepine;rotraxate; setiptiline; siltenzepine; sofalcone; sucralfate;sucrosofate; sulglicotide; telenzepine; teniloxazine; teprenone;tiopropamine; tolimidone; triletide; tritiozine; troxipide; UH-AH-37;zolenzepine; zolimidine.

Agents for Treating Urolithiasis:

benzoic acid; cysteamine; cysteamine; tricitrates.

Virustatic Agents:

abacavir; acemannan; aciclovir; adefovir; alovudine; alvircept sudotox;atevirdine; amantadine; aranotin; arildone; atevirdine; avridine;BW-935-U83; calanolide B; cidofovir; cipamfylline; cytarabine; DAPD;delavirdine; desciclovir; didanosine; disoxaril; DPC-083; edoxudine;efavirenz; emivirine; enviradene; enviroxime; famciclovir; famotine;flacitabine; fialuridine; fosarilate; foscarnet sodium; fosfonet sodium;ganciclovir; GW-420867X; idoxuridine; kethoxal; L-697661; lamivudine;lobucavir; memotine; methisazone; nevirapine; NSC-678323; penciclovir;pirodavir; ribavirin; rimantadine; S-1153; saquinavir; somantadine;sorivudine; statolon; stavudine; talviraline; thioctic acid; tilorone;trifluridine; trovirdine; U-93923; valaciclovir; vidarabine; vidarabine;vidarabine; viroxime; zalcitabine; zidovudine; zinviroxime.

Active Ingredients for Treating Benign Prostate Hyperplasia:

alfuzosin; CEP-701; doxazosin; dutasteride; FK-143; GI-231818;GYKI-16084; levormeloxifene; pirfenidone; RS-97078; tamsulosin;sitoglusid.

Active Ingredients for Treating Osteoporosis: alendronic acid;butedronic acid; clodronic acid; EB-1053; etidronic acid; ibandronicacid; incadronic acid; medronic acid; minodronic acid; neridronic acid;olpadronic acid; oxidronic acid; pamidronic acid; piridronic acid;ranelic acid; risedronic acid; tiludronic acid; YM-529; zoledronic acid.Carbonic Anhydrase Inhibitors:

acetazolamide; AL4414A; diclofenamide; dorzolamide; methazolamide;sezolamide; sulocarbilate.

Antiarrhythmics:

abanoquil; ACC-9164; acecainide; actisomide; adenosine; ajmaline;alinidine; almokalant; alprafenone; amafolone; ambasilide; ameltolide;amiodarone; aprindine; aprindine; artilide; asocainol; AWD-G-256;azimilide; benderizine; benrixate; benzodioxine; berlafenone;bertosamil; bidisomide; bisaramil; BRL-32042; bucainide; bucromarone;bunaftine; buquineran; butobendine; butoprozine; capobenic acid;carbizocaine; carcainium chloride; cariporide; carocainide; cercainide;cibenzoline; cifenline; ciprafamide; CL-284027; clamikalant; clofiliumphosphate; CV-6402; CVT-510; cyclovirobuxine-D, D-230; detaJmiumbitartrate; disobutamide; dexsotalol; dioxadilol; diprafenone;disobutamide; disopyramide; dofetilid; drobuline; dronedarone;droxicainide; E047/1; E-0747; E4031; edifolone; emilium tosilate;emopamil; encainide; eproxindine; erocainide; ersentilide; fepromide;flecainide; fluzoperide; gallanilide; glemanserin; guafecainol;GYKI-23107; GYKI-38233; heptacaine; hydroxyfenone; ibutiide;indecainide; ipazilide; itrocainide; ketocainol; L-702958; L-706000;levosemotiadil; lorajmine; lorcainide; meobentine; mexiletine;milacainide; modecainide; moracizine; moxaprindine; murocainide;nibentan; nicainoprol; nipekalant; nofecalnide; oxiramide; palatrigine;penticainide; pentisomide; pilsicainide; pirmenol; pirolazamide;prajmalium bitartrate; pranolium chloride; prifuroline; procainamide;propafenone; pyrinoline; quinacainol; quindonium bromide; quinidine;recainam; rilozarone; risotilide; ronipamil; ropitoin; sematilide;sinomenine; solpecainol; sparteine; stirocainide; stobadine; SR47063;sulamserod; suricainide; tedisamil; terikalant; tiracizine; tocainide;tosifen; transcainide; trecetilide; zocainone.

Cardiotonics:

acadesine; acetyidigitoxin; acetyldigoxin; acrihellin; actodigin;adibendan; amrinone; amselamine; arbutamine; arpromidine; AWD-122-239;bemoradan; bucladesine; butopamine; carbazeran; cariporide; carperitide;carsatrin; CGS-13928C; cilobradine; CK-2130; CK-2289; colforsin;CV-6402; denopamine; deslanoside; dexrazoxane; digitalis; digitoxin;digoxin; dobutamine; dobutamine; docarpamine; domipizone; dopexamine;doridosine; doxaminol; DPI-201-106; draflazine; eniporide; enoximone;ER-21355; evodiamine; falipamil; FK-664; fosfructose; FR-113453;FR-46171; gapromidine; gitaloxin; gitoformate; JP-1-468; GP-1-531;GP-668; heptaminol; higenamine; ibopamine; imazodan; indolidan;isamoltan; isomazole; levacecarnine; levdobutamine; levosimendan;limaprost; linsidomine; lixazinone; MCI-154; medorinone; meproscillarin;meribendan; metildigoxin; mildronate; milrinone; mioflazine; mixidine;MS-857; nanterinone; neraminol; NKH-477; olprinone; OPC-18750;otenzepad; oxfenicine; peirinone; pengitoxin; pentrinitrol; peruvosid;pimobendan; piroximone; pirsidomine; prinoxodan; prisotinol;propionylcamitine; proscillaridin; quazinone; quazodine; quindoniumbromide; ramnodigin; revizinone; saterinone; siguazodan; simendan;sulmazole; thevetosid; toborinone; ubidecarenone; vesnarinone; VPA-985.

Choleretic Agents:

alibendol; azintamide; boldine; cicloxilic acid; cinametic acid;clanobutin; dehydrocholic acid; dibuprol; epomediol; exiproben;febuprol; fencibutirol; fenipentol; hexacyprone; hymecromone; menbutone;moquizone; piprozolin; prozapine; sincalide; tenylidone; terbuprol;tocamphyl; trepibutone.

Cholinergic Agents:

acedidine; bethanechol chloride; carbachol; demecarium bromide;dexpanthenol; echothiophate iodide; isoflurophate; methacholinechloride; neostigmine bromide; neostigmine methylsulfate; physostigmine;physosugmine salicylate; physosugmine sulfate; pilocarpine; pilocarpine;pilocarpine nitrate; pyridostigmine bromide.

Cholinergic Agonists:

xanomeline; xanomeline tartrate.

Cholinesterase Inhibitors:

acetohydroxamic acid; DMPS; amiphenazole; obidoxime chloride;pralidoxime chloride; pralidoxime iodide; pralidoxime mesilate.

Coccidiostats:

aklomide; amidapsone; amprolium; arprinocid; bitipazone; buquinolate;ciadox; clazuril; dopidol; decoquinate; diciazuril; dinitolamide;dinsed; halofuginone; letrazuril; narasin; nequinate; nicarbazine;nifursemizone; ponazuril; proquinolate; robenidine; semduramicin;sulazuril; sulfanitran; tiazuril; tosulur.

Diuretics:

acetazolamide; acetothiazide; alipamide; altizide; amanozine;ambuphylline; ambuside; amiloride; aminometradine; amisometradine;ampyrimine; apaxifylline; azolimine; azosemide; bemetizide; bemitradine;bendroflumethiazide; benzamil; benzolamide; benzthiazide;benzylhydrochlorothiazide; besulpamide; besunide, brocrinat; bumetanide;butizide; canrenoic acid; carmetizide; chlorazanil; chlorothiazide;chlorthalidone; cicletanine; clazolimine; clopamide; clorexolone;CVT-124; dicirenone; disulfamide; etamiphylline; ethacrynate sodium;ethacrynic acid; etofylline; etozolin; fenquizone; FK-352; FR-113453;furosemide; hydrochlorothiazide; hydroflumethiazide; indacrinone;indapamide; isosorbide; KW-3902; lemidosul; mannitol; mebutizide;mefruside; methalthiazide; methazolamide; methydothiazide; meticrane;metolazone; muzolimine; niravoline; OPC-31260; oxprenoate; ozolinone;paraflutizide; penflutizide; piretanide; polythiazide; canrenoate;propazolamide; prorenoate; prorenone; pytamine; quincarbate;quinethazone; RPH-2823; S-8666; sitalidone; spironolactone; spirorenone;spiroxasone; SR48692; sulciamide; sulicrinat; sulocarbilate; sulosemide;sumetizide; teclothiazide; tiamizide; tienilic acid; torsemide;triamterene; trichlormethiazide; triflocin; tripamide; TRK-820;ularitide; urea; xipamide.

Ectoparasiticides:

carbaril; clidafidine; cypermethrin; eprinomectin; fenclofos;fenvaierate; ivermectin; lindane; moxidectin; nifluridide; permethrin;temefos.

Emetics:

apomorphine.

Enzyme Inhibitors:

acetohydroxamic acid; alrestatin sodium; aprotinin; benazepril;benazeprilat; benurestat; bromocriptine; bromocriptine mesilate;cilastatin sodium; flurofamide; lergotrile; lergotrile mesilate;levcycloserine; libenzapril; pentopril; pepstatin; perindopril;polignate sodium; sodium amylosulfate; sorbinil; spirapril; spiraprilat;taleranol; teprotide; tolfamide; zofenopril calcium.

Estrogens:

chlorotrianisene; dienestrol; diethylstilbestrol; diethylstilbestroldiphosphate; equilin; epimestrol; estradiol; estradiol cypionate;estradiol enanthate; estradiol undecylate; estradiol valerate;estrazinol hydrobromide; estriol; estrofurate; estrogens, conjugated;estrogens, esterified; estrone; estropipate; ethinyl estradiol;fenestrel; mestranol; nylestriol; quinestrol

Fibrinolytics:

acexamic acid; amediplase; anistreplase; aprotinin; bisobrin lactate;brinase; brinolase; camostat; fibrinolysin; inicarone; iquindamine;nattokinase; pamiteplase; picotamide; staplabin; streptokinase; taurine;tizabrin; tranexamic acid;

Free-radical Scavenger:

pegorgotein.

Motility-increasing Active Ingredients:

cisapride (Propulsid); metoclopramide (Reglan); hyoscyamine (Levsin).

Glucocorticosteroids:

acrocinonide; alclometasone; algestone acetonide; amcinafal; amcinafide;amcinonide; amebucort; amelometasone; beclomethasone dipropionate;bendazacort; betamethasone; betamethasone acetate; betamethasonebenzoate; betamethasone diproplonate; betamethasone sodium phosphate;betamethasone valerate; budesonide; butixocort; butxocort propionate;CGP-13774; ciclesonide; ciclometasone; ciprocinonide; clobetasol;clobetasol 17-propionate; clobetasone; clocortolone acetate;clocortolone pivalate; cloprednol; cloticasone; cloticasone propionate;CMJ; cormetasone; corticotropin; corticotropin; corticotropin zinchydroxide; cortisone acetate; cortisuzol; cortivazol; deflazacort;deprodone; deprodone propionate; descinolone acetonide; desonide;desoximetasone; desoxycortone; dexamethasone; dexamethasone acefurate;dexamethasone sodium phosphate; dexbudesonide; dichlorisone;diflorasone; diflucortolone; diflucortolone pivalate; difluprednate;dimesone; domoprednate; doxibetasol; drocinonide; FSDCICM; fluazacort;fluclorolone acetonide; flucloronide; fludrocortisone; fludroxycortide;flumetasone; flumetasone pivalate; flumoxonide; flunisolide;fluocinolone acetonide; fluocinonide; fluocortin; fluocortin butyl;fluocortolone; fluocortolone caproate; fluorometholone; flupamesone;fluperolone acetate; fluprednidene; fluprednisolone; fluprednisolonevalerate; flurandrenolide; fluticasone; fluticasone propionate;formocortal; gestonorone caproate; GW-215864X ; GW-250945; halcinonide;halocortolone; halometasone; halopredone acetate; hydrocortamate;hydrocortisone; hydrocortisone acetate; hydrocortisone aceponate;hydrocortisone buteprate; hydrocortisone butyrate; hydrocortisoneenbutate; hydrocortisone sodium phosphate; hydrocortisone sodiumsuccinate; hydrocortisone valerate; icometasone enbutate; isoflupredone;isoprednidene; itrocinonide; locicortolone; locicortolone dicibate;loteprednol etabonate; mazipredone; meclorisone; medrysone;meprednisone; methylprednisolone; methylprednisolone acetate;methylprednisoloxime sodium phosphate; methylprednisolone sodiumsuccinate; mometasone furoate; naflocort; nivacortol; nivazol;paramethasone acetate; prednazate; prednazoline; prednicarbate;prednisolamate; prednisolone; prednisolone acetate; prednisolonefamesylate; prednisolone hemisuccinate; prednisolone sodium phosphate;prednisolone sodium succinate; prednisolone tebutate; prednisone;prednylidene; pregnenolone; prednival; procinonide; resocortol;rimexolone; rofleponide; TBI-PAB; ticabesone propionate; timobesone;tipredane; tixocortol; tixocortol pivalate; tralonide; triamcinolone;triamcinolone acetonide; triamcinolone acetonide sodium; triamcinolonebenetonide; triamcinolone diacetate; triamcinolone furetonide;triamcinolone hexacetonide; triclonide; ulobetasol.

Hemostatics:

aminocaproic acid; oxamarin; sulmarin; thrombin; tranexamic acid.

Hormones: diethylstilbestrol; progesterone; 17-hydroxy progesterone;medroxyprogesterone; norgestrel; norethynodrel; estradiol; megestrol(Megace); norethindrone; levonorgestrel; ethyndiol; ethinyl estradiol;mestranol; estrone; equilin; 17-alpha-dihydroequilin; equilenin; 17alpha dihydroequilenin; 17-alpha-estradiol; 17-beta-estradiol;leuprolide (lupron); glucagon; testolactone; clomiphene; han memopausalgonadotropins; human chorionic gonadotropin; urofollitropin;bromocriptine; gonadorelin; luteinizing hormone releasing hormone andanalogs; gonadotropins; danazol; testosterone; dehydroepiandrosterone;androstenedione; dihydroestosterone; relaxin; oxytocin; vasopressin;folliculostatin; follicle regulatory protein; gonadoctrinins; oocytematuration inhibitor; insulin growth factor; follicle stimulatinghormone; luteinizing hormone; tamoxifen; corticorelin ovine triftutate;cosyntropin; metogest; pituitary, posterior; seractide acetate;somalapor; somatrem; somatropin; somenopor; somidobove.HMG-CoA Reductase Inhibitors:

lovastatin (Mevacor); simvastatin (Zocor); pravastatin (Pravachol);fluvasatin (Lescol).

Immunomodulators:

dimepranol acedoben; imiquimod; interferon beta-lb; lisofylline;mycophenolate mofetil; prezatide copper acetate.

Immunoregulators:

azarole; fanetizole mesilate; frentizole; oxamisole; ristianolphosphate; thymopentin; tilomisole.

Immunostimulants:

loxoribine; teceleukin.

Immunosuppressants:

azathioprine; azathioprine sodium; cyclosporine; daltroban; gusperimustrihydrochloride; sirolimus; tacrolimus.

Active Ingredients for Treating Impotence:

abanoquil; alprostadil; amlodipine; BMS-193884; delequamine; doxazosin,E-4010; glycerol trinitrate; IC-351; melanotan II; minoxidil;nitraquazone; papaverine; phenoxybenzamine; prazosin; quinelorane;sildenafil; UK-114542; urapidil; vardenafil; VIP; yohimbin;

LHRH Antagonists:

deslorelin; goserelin; histrelin; lutrelin acetate; nafarelin acetate.

Hepatoprotectant:

malotilate.

Luteolytics:

fenprostalene.

Cerebrotonics:

aloracetam; alvameline; aniracetam; apaxifylline; aptiganel; azetirelin;brovincamine; cebaracetam; cevimeline; CI-844; CI-933; demiracetam;dimoxamine; donepezil; dupracetam; edaravone; ensaculin; fasoracetam;FK-960; gavestinel; igmesine; muracetam; IOS-11212; JTP4819; KST-5410;leteprinim; ligustizine; linopirdine; MCI-225; milameline; MKC-231;NDD-094; nebracetam; nicoracetam; nizofenone; ONO-1603; OP-2507;OPC-14117; oxiracetam; pikamilone; piracetam; piraxelate; pirglutargine;pramiracetam; pyritinol; quilostigmine; ribaminol; rivastigmine;rolziracetam; sabcomeline; sapropterin; SIB-1553A; sibopirdine;sipatrigine; SM-10888; SNK-882; SR-46559-A; stacofylline; T-588; T-82;TAK-147; talsaclidine; taltirelin; tamitinol; tenilsetam; vinconate;vinpocetine; xaliproden; xanomeline; YM-796; YM-900; Z-321; zifrosilone.

Mucolytics:

acetylcysteine; adamexine; ambroxol; bencisteine; bromhexine;brovanexine; carbocysteine; cartasteine; cistinexine; dacisteine;danosteine; dembrexine; domiodol; erdosteine; erythromycin salnacedin;erythromycin stinopate; guaimesal; IDB-1031; isalsteine; letosteine;mecysteine; mesna; midesteine; moguisteine; neltenexine; nesosteine;omonasteine; oxabrexine; prenisteine; salmisteine; stepronin; tasuldine;taurosteine; telmesteine; tiopronin.

Mydriatics:

berefrine.

Neuroprotective Agents:

dizocilpine maleate.

NMDA Antagonists:

ACPC; aptiganel; BMY-14802; CGP-37849; CP-101606; dizocilpine; EAA-090;eliprodil; felbamate; FPL-12495; gavestinel; harkoseride; HU-211;ipenoxazone; L-695902; lanicemine; licostinel; ligustizine; midafotel;milnacipran; nebostinel; remacemide; selfotel; seratrodast; spermidine;spermine; UK-240255; ZD-9379.

Nonhormonal Steroid Derivatives:

pregnenolone succinate.

Oxytocics:

carboprost; carboprost methyl; carboprost tromethamine; dinoprost;dinoprost tromethamine; dinoprostone; ergonovine maleate; meteneprost;methylergonovine maleate; oxytocin; sparteine sulfate.

Plasminogen Activators:

alteplase; urokinase.

PAF Antagonists:

lexipafant.

Aggregation Inhibitors:

acadesine; beraprost; beraprost sodium; ciprostene calcium; itazigrel;lifarizine; oxagrelate.

Progestins:

algestone acetophenide; amadinone acetate; anagestone acetate;chlormadinone acetate; cingestol; clogestone acetate; clomegestoneacetate; desogestrel; dimethisterone; dydrogesterone; ethynerone;ethynodiol diacetate; etonogestrel; flurogestone acetate; gestaclone;gestodene; gestonorone caproate; gestrinone; haloprogesterone;hydroxyprogesterone caproate; levonorgestrel; lynestrenol; medrogestone;medroxyprogesterone acetate; methynodiol diacetate; norethindrone;norethindrone acetate; norethynodrel; norgestimate; norgestomet;norgestrel; oxogestone phenproplonate; progesterone; quingestanolacetate; quingestrone; tigestol.

Prostate Growth Inhibitors:

pentomone.

Prothyrotropin:

protirelin.

Psychotropic Agents:

minaprine.

Calcium Regulators:

alfacalcidol; calcifediol; calcipotriol; calcitonin; calcitriol;dihydrotachysterol; doxercalciferol; falecalcitriol; lexacalcitol;maxacalcitol; secalciferol; seocalcitol; tacalcitol;

Relaxants:

adiphenine; alcuronium chloride; aminophylline; azumolene sodium;baclofen; benzoctamine; carisoprodol; chlorphenesin carbamate;chlorzoxazone; cinflumide; cinnamedrine; clodanolene; cyclobenzapine;dantrolene; dantrolene sodium; fenalamide; fenyripol; fetoxylate;flavoxate; fletazepam; flumetramide;-flurazepam; hexafluorenium bromide;isomylamine; lorbamate; mebeverine; mesuprine; metaxalone;methocarbamol; methixene; nafomine malate; nelezaprine maleate;papaverine; pipoxolan; quinctolate; ritodrine; ritodrine; rolodine;theophylline sodium glycinate; thiphenamil; xilobam.

Scabicides:

amitraz; crotamiton.

Sclerosing Agents:

clobenoside; ethanolamine oleate; morrhuate sodium; olamine;tribenoside.

Sedatives:

propiomazine.

Hypnotics/sedatives:

allobarbital; alonimid; alprazolam; amobarbital sodium; bentazepam;brotizolam; butabarbital; butabarbital sodium; butalbital; capuride;carbocloral; chloral betaine; chloral hydrate; chlordiazepoxide;cloperidone; clorethate; cyprazepam; dexclamol; diazepam;dichloralphenazone; estazolam; ethchlorvynol; etomidate; fenobam;flunitrazepam; fosazepam; glutethimide; halazepam; lormetazepam;mecloqualone; meprobamate; methaqualone; midaflur; paraldehyde;pentobarbital; pentobarbital sodium; perlapine; prazepam; quazepam;reclazepam; roletamide; secobarbital; secobarbital sodium; suproclone;thalidomide; tracazolate; trepipam maleate; triazolam; tricetamide;triclofos sodium; trimetozine; uldazepam; zaleplon; zolazepam; zolpidemtartrate.

Selective Adenosine A1 Antagonists:

apaxiylline

Serotonin Antagonists:

altanserin tartrate; amesergide; ketanserin; ritanserin, tropanserin

Serotonin Inhibitors:

cinanserin; fenclonine; fonazine mesilate; xylamidine tosylate.

Stimulants:

amfonelic acid; amphetamine sulfate; ampyzine sulfate; arbutamine;azabon; caffeine; ceruletide; ceruletide diethylamine; cisapride;dazopride fumarate; dextroamphetamine; dextroamphetamine sulfate;difluanine; dimefline; doxapram; etryptamine acetate; ethamivan;fenethylline; flubanilate; flurothyl; histamine phosphate; indriline;mefexamide; methamphetamine hydrochlo ride; methylphenidate; pemoline;pyrovalerone; xamoterol; xamoterol fumarate.

Suppressants:

amflutizole; coxchicine; tazofelone.

Active Ingredients for Treating Symptomatic Multiple Sclerosis:

fampridine.

Synergistic Agents:

proadifen.

Thyroid Hormones:

levothyroxine sodium; liothyronine sodium; liotrix.

Thyroid Inhibitors:

methimazole; propyithiouracil.

Thyromimetics:

thyromedan.

Tranquilizers:

bromazepam; buspirone; chlordiazepoxide; clazolam; clobazam; clorazepatedipotassium; clorazepate monopotassium; demoxepam; dexmedetomidine;enciprazine; gepirone; hydroxyphenamate; hydroxyzine; hydroxyzinepamoate; ketazolam; lorazepam; lorzafone; loxapine; loxapine succinate;medazepam; nabilone; nisobamate; oxazepam; pentabamate; pirenperone;ripazepam; roliprarn; sulazepam; taciamine; temazepam; triflubazam;tybamate; vainoctamide.

Agent for Treating Cerebral Ischemia:

dextrorphan.

Agent for Treating Paget's Disease:

tiludronate disodium.

Uricosuric Agents:

benzbromarone; irtemazole; probenecid; sulfinpyrazone.

Vasoconstrictors:

adrenalone; amidefrine mesilate; angiotensin amide; cafaminol;cilutazolin; clonazoline; corbadrine; domazoline; epinephrine;epinephryl borate; fenoxazoline; indanazoline; mephentermine;methysergide; metizoline; metrafazoline; naphazoline; riemazoline;oxedrine; oxymetazoline; phenamazoline; phenylephrine;phenylpropanolamine polistirex; tefazoline; tetryzoline; tinazoline;tramazoline; xylometazoline.

Vasodilators:

alprostadil; azaclorzine; bamethan sulfate; bepridil; buterizine;cetiedil citrate; chromonar; clonitrate; diltiazem; dipyridamole;droprenilamine; erythrityl tetranitrate; felodipine; flunarizine;fostedil; hexobendine; inositol niacinate; iproxamine; isosorbidedinitrate; isosorbide mononitrate; isoxsuprine; lidoflazine; mefenidil;mefenidil fumarate; mibefradil dihydrochloride; mioflazine; mixidine;nafronyl oxalate; nicardipine; nicergoline; nicorandil; nicotinylalcohol; nifedipine; nimodipine; nisoldipine; oxfenicine; oxprenolol;pentaerythritol tetranitrate; pentoxifylline; pentrinitrol; perhexilinemaleate; pindolol; pirsidomine; prenylamine; propatyl nitrate;suloctidil; terodiline; tipropidil; tolazoline; xanthinol niacinate.

Active Ingredients for Wound Healing:

ersofermin.

Xanthine Oxidase Inhibitors:

allopurinol; oxypurinol

In a preferred embodiment of the invention, the active ingredient is aPDE (phosphodiesterase) inhibitor, particularly preferably PDE 4inhibitor, especiallyN-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide(INN: roflumilast) its N-oxide or a pharmacologically suitable salt ofroflumilast or of its N-oxide. The preparation ofN-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide,its pharmacologically suitable salts and its N-oxide, and the use ofthese compounds as phosphodiesterase (PDE) 4 inhibitors is described inthe international application WO95/01338. In a particularly preferredembodiment of the invention, the active ingredient is aphosphodiesterase (PDE) 3/4 inhibitor, in particular(−)-cis-9-ethoxy-8-methoxy-6-(4-diisopropylaminocarbonylphenyl)-2-methyl-1,2,3,4,4a,10b-hexahydrobenzo[c][1,6]naphthyridine(INN: pumafentrine). The preparation of(−)-cis-9-ethoxy-8-methoxy-6-(4-disopropylaminocarbonylphenyl)-2-methyl-1,2,3,4,4a,10b-hexahydrobenzo[c][1,6]naphthyridineand its pharmacologically suitable salts, and the use of this compoundas phosphodiesterase (PDE) 3/4 inhibitor is described in theInternational application WO98/21208.

The matrix of the invention is outstandingly suitable as dosage form foractive ingredients from the class of substances known as reversible H⁺,K⁺-ATPase inhibitors, which are also referred to as reversible protonpump inhibitors or APAs (acid pump antagonists). Reversible proton pumpinhibitors or APAs are disclosed, for example, in the patent documentDE-A 3917232, EP-A-0399267, EP-A-0387821, JP-A-3031280, JP-A-2270873,EP-A-0308917, EP-A-0268989, EP-A-0228006, EP-A-0204285, EP-A-0165545,EP-A-0125756, EP-A-0120589, EP-A-0509974, DE-A3622036, EP-A-0537532,EP-A-0535529, JP-A-3284686, JP-A-3284622, U.S. Pat. No. 4,833,149,EP-A-0261912, WO-A-9114677, WO-A-9315055, WO-A-9315071, WO-A-9315056,WO-A-9312090, WO-A-9212969, WO-A-9118887, EP-A-0393926, EP-A-0307078,U.S. Pat. No. 5,041,442, EP-A-0266890, WO-A-9414795, EP-A-0264883,EP-A-0033094, EP-A-0259174, EP-A-0330485, WO-A-8900570, EP-A-0368158,WO-A-9117164, WO-A-9206979, WO-A-9312090, WO-A-9308190, U.S. Pat. No.5,665,730, DE-A 3011490, U.S. Pat. No. 4,464,372, EP-A-0068378,WO-A-9424130, U.S. Pat. No. 5,719,161, U.S. Pat. No. 6,124,313,WO-A-9527714, WO-A-9617830, WO-A-9837080, WO-A-9955705, WO-A-9955706,WO-A-0010999, WO-A-0011000, especially in the documents WOA-9842707,WO-A-9854188, WO-A-0017200, WO-A-0026217 and WO-A-0063211, and in otherpatent documents which relate to compounds which inhibit gastric acidsecretion and have a quinoline, imidazo[1,2-a]pyridine,7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine or7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine basic structure.

Examples of reversible proton pump inhibitors or APAs which should bementioned as preferred are, inter alia:

-   AU-461    [2-[1-(2-methyl-4-methoxyphenyl)-6-(2,2,2-trifluoroethoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]quinolin-4-ylamino]-1-ethanol],-   DBM-819    [3-[1-(4-methoxy-2-methylphenyl)-6-methyl-2,3-dihydro-1H-pyrrolo-[3,2-c]quinolin-4-ylamino]-1-propanol],-   KR-60436    [2-[1-(4-methoxy-2-methylphenyl)-6-(trifluoromethoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]quinolin-4-ylamino]ethanol],-   R-105266; YJA-20379-8 [(+)-1-[8-ethoxy-4-[(1    (R)-phenylethyl)amino]-1,7-naphthyridin-3-yl]-1-butanone],-   8-(2-methoxycarbonylamino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine,-   3-hydroxymethyl-8-(2-methoxycarbonylamino-6-methylbenzylamino)-2-methylimidazo[1,2-a]-pyridine,-   3-hydroxymethyl-8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methylimidazo[1,2-a]-pyridine,-   8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2,3-dimethylimidazo[1,2-a]pyridine,-   8-(2-tert-butoxycarbonylamino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine,-   8-(2-tert-butoxycarbonylamino-6-methylbenzyloxy)-2,3-dimethylimidazo[1,2-a]pyridine,-   8-(2-ethoxycarbonylamino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine,-   8-(2-isobutoxycarbonylamino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine,-   8-(2-isopropoxycarbonylamino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine,-   8-(2-tert-butoxyarbonylamino-6-methylbenzylamino)-3-hydroxymethyl-2-methylimidazo[1,2-a]-pyridine,-   8-(2-tert-butoxycarbonylamino-6-methylbenzyloxy)-3-hydroxymethyl-2-methylimidazo[1,2-a]-pyridine,-   8(2-[(2-methoxyethoxy)carbonylamino]-6-methylbenzyloxy)-2-methylimidazo[1,2-a]pyridine-3-methanol,-   8(2-[(2-methoxyethoxy)carbonylamino]-6-methylbenzylamino)-2-methylimidazo[1,2-a]-pyridine-3-methanol,-   8-(2-[(2-methoxyethoxy)carbonylamino]-6-methylbenzylamino]2,3-dimethylimidazo[1,2-a]-pyridine,-   8-(2-[(2-methoxyethoxy)carbonylamino]-6-methylbenzyloxy)-2-methylimidazo[1,2-a]pyridine-3-methanol,-   8-(2-[(2-methoxyethoxy)carbonylamino]-6-methylbenzylbenzyloxy-2,3-dimethylimidazo[1,2-a]pyridine,-   3-hydroxymethyl-2-methyl-8-benzyloxyimidazo[1,2-a]pyridine,-   3-hydroxymethyl-2-trifluoromethyl-8-benzyloxyimidazo[1,2-a]pyrldine,-   1,2-dimethyl-3-cyanomethyl-8-benzyloxyimidazo[1,2-a]pyrldine,-   2-methyl-3-cyanomethyl-8-benzyloxyimidazo[1,2-a]pyridine,-   3-butyryl-8-methoxy-4-(2-methylphenylamino)quinoline,-   3-butyryl-8-hydroxyethoxy-4-(2-methylphenylamino)quinoline,-   3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine,-   3-hydroxymethyl-2-methyl-9-(4-fluorophenyl)-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine,-   (+)-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine,-   (−)-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine,-   8-(2-ethyl-6-methylbenzylamino)-3-(hydroxymethyl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide,-   N-(2-hydroxyethyl)-8-(2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-N,2,3-trimethylimidazo[1,2-a]pyridine6-carboxamide,-   8-(2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-4-fluoro-6methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(4-fluoro-2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2,6-diethylbenzylamino)-2,3-dimethylimidazol[1,2-a]pyridine-4-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-N-(2-hydroxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-N-(2-methoxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-3-(hydroxymethyl)-2-methylimidazo[1,2-a]pyridine-6-carboxamide,-   N-(2-hydroxyethyl)-8-(2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-N,2,3-trimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl4-fluoro-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(4-fluoro-2,6-dimethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2,6-diethylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,-   8-(2-ethyl-6-methylbenzylamino)-N-(2-hydroxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,    and-   8-(2-ethyl-6-methylbenzylamino)-N-(2-methoxyethyl)-2,3-dimethylimidazo[1,2-a]pyridine-6-carboxamide,    and, in particular,-   7,8-dihydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   7-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   9-(2-chlorophenyl)-7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   9-(2,6-dichlorophenyl)-7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   9-(2-trifluoromethylphenyl)-7-hydroxy-2,3-dimethyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   8-hydroxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one,-   (8R,9R)-3-formyl-8-hydroxy-2-methyl-7-oxo-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   (7R,8R,9R)-3-hydroxymethyl-7,8-dihydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthridine,-   (7S,8R,9R)-7,8-isopropylidenedioxy-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine,-   8,9-trans-8-hydroxy-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]-pyridine,-   8,9-cis-8-hydroxy-3-hydroxymethyl-2-methyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]-pyridine,-   8,9-trans-3-hydroxymethyl-2-methoxy-2-methyl-9-phenyl-7H-8,9-dihydropyrano-[2,3-c]imidazo[1,2-a]-pyridine,-   8,9-cis-3-hydroxymethylmethoxy-2-methyl-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]-pyridine,-   8,9-trans-8-ethoxy-3-hydroxymethyl-2-methyi-9-phenyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]-pyridine,-   8-hydroxy-7-oxo-9-phenyl-2,3-dimethyl-7H-8,9-dihydropyrano[2,3-c]imidazo[,2-a]pyridine,-   7,8-dihydroxy-9-phenyl-2,3-dimethyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine,-   7-hydroxy-9-phenyl-2,3-dimethyl-7H-8,9-dihydropyrano[2,3-c]imidazo[1,2-a]pyridine,-   (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydroimldazo[1,2-h]-[1,7]naphthyridine,-   (7S,8S,9S)-2,3-dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7R,8S,9S)-2,3-dimethyl-8-hydroxy-7-methoxy-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7R,8R,9R)-2,3-dimethyl-7-ethoxy-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-7-ethoxy-8-hydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8S,9S)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7R,8S,9S)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-9-phenyl-7-(2-propoxy)-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7R,8R,9R)-2,3-dimethyl-7,8-dimethoxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridine,-   (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylthioethyloxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylthioethyfoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylsulfinylethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methylsulfinylethoxy)9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,-   (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(ethylthio)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridine,-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(ethylthio)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]-naphthyridine,-   (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2,2,2-trifluoroethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine    and-   (7S,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2,2,2-trifluoroethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine,    and very particularly-   (7R,8R,9R)-2,3-dimethyl-7,8-dihydroxy-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine    and-   (7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydrolmidazo[1,2-h]-[1,7]naphthyridine.

The matrix of the of the invention is also outstandingly suitable asdosage form for active ingredients from the class of substances known asacid-labile H⁺, K⁺-ATPase inhibitors, which are also referred to asirreversible proton pump inhibitors. Acid-labile proton pump inhibitors(H⁺/K⁺-ATPase inhibitors) which may be particularly mentioned for thepurpose of the present invention are substitutedpyridin-2-ylmethylsulfinyl-1H-benzimidazoles as disclosed, for example,in EP-A-0 005 129, EP-A-0 166 287, EP-A 0 174 726, EP-A-0 184 322,EP-A-0 261 478 and EP-A-0 268 956. Those which may be mentioned aspreferred in this conenction are5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylsulfinyl]-1H-benzimidazole(INN: omeprazole),5-difluoromethoxy-2-[(3,4-dimethoxy-2-pyridinyl)-methylsulflny]-1H-benzimidazole(INN: pantoprazole),2-[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl)methylsulfinyl]-1H-benzimidazole(INN: lansoprazole) and2-{[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl}-1H-benzimidazole(INN: rabeprazole). Further acid-labile proton pump inhibitors, forexample substituted phenylmethylsulfinyl-1H-benzimidazoles,cycloheptapyridin-9-ylsulfinyl-1H-benzimidazoles orpyridin-2-ylmethylsulfinylthienoimidazoles, are disclosed in DE-A-35 31487, EP-A-0 434 999 and EP-A-0 234 485 respectively. Examples which maybe mentioned are2-[2-(N-isobutyl-N-methylamino)benzylsulfinyl]benzimidazole (INN:leminoprazole) and2-(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylsulfinyl)-1H-benzimidazole(INN: nepaprazole). The acid-labile proton pump inhibitors are chiralcompounds. The term acid-labile proton pump inhibitor also encompassesthe pure enantiomers of the acid-labile proton pump inhibitors and theirmixtures in any mixing ratio. Pure enantiomers which may be mentioned byway of example are5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole(INN: esomeprazole) and (−)-pantoprazole. The acid-labile proton pumpinhibitors are moreover present as such or, preferably, in the form oftheir salts with bases. Examples of salts with bases which may bementioned are sodium, potassium, magnesium or calcium salts. If theacid-labile proton pump inhibitors are isolated in crystalline form,they may contain variable amounts of solvent The term acid-labile protonpump inhibitor therefore also represents according to the invention allsolvates, in particular all hydrates, of the acidlabile proton pumpinhibitors and their salts. Such a hydrate of the salt of an acid-labileproton pump inhibitor with a base is disclosed, for example, inWO91/19710. Acid-labile proton pump inhibitors which may be mentioned asparticularly preferred are pantoprazole sodium sesquihydrate(=pantoprazole sodium×1.5H₂O), (−)-pantoprazole sodium sesquihydrate,pantoprazole magnesium dihydrate, omeprazole magnesium, omeprazole andesomeprazole.

In another preferred embodiment of the Invention, the active ingredientis a glucocorticosterold, in particular ciclesonide.

The active ingredients may, depending on the nature of the activeingredient, also be present in the preparations of the invention in theform of a salt of the active ingredient. Particular mention may be madeof the pharmacologically suitable salts of the inorganic and organicacids normally used in pharmaceutical technology. Suitable as such are,on the one hand, water-soluble and water-insoluble acid addition saltswith acids such as, for example, hydrochloric acid, hydrobromic acid,phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid,D-gluconic acid, benzoic acid, 2-(4-hydroxybenzoyl)benzoic acid, butyricacid, sulfosalicylic acid, maleic acid, lauric acid, malic acid, fumaricacid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearicacid, toluene sulfonic acid, methanesulfonic acid or3-hydroxy-2-naphthoic acid, the acids being employed for preparing thesalts in the equimolar ratio of amounts, or a ratio differingtherefrom,—depending on whether the acid is monobasic or polybasic anddepending on which salt is required.

On the other hand, salts with bases are also suitable. Examples of saltswith bases which may be mentioned are alkali metal (lithium, sodium,potassium) or calcium, aluminum, magnesium, titanium, ammonium,megiumine or guanidinium salts, the bases being employed for preparingthe salts also in the equimolar ratio of amounts or in a ratio differingtherefrom.

The skilled worker is aware that active ingredients and their salts may,if they are isolated, for example, in crystalline form, contain variousamounts of solvents. The active ingredients will therefore also bepresent in the preparations of the Invention in the form of solvatesand, in particular, hydrates, and in the form of solvates and, inparticular, also hydrates of the salts of the active ingredients.

The active ingredients may also be chiral compounds. It is thereforealso possible for the pure enantiomers of the active ingredients andmixtures thereof in any mixing ratio to be present in the preparationsof the invention.

The fatty alcohol is preferably a linear, saturated or unsaturatedprimary alcohol with 10–30 carbon atoms. It is preferably a primaryalcohol with 10 to 18 carbon atoms in linear chains. Examples of fattyalcohols which may be mentioned are cetyl alcohol, myristyl alcohol,lauryl alcohol or stearyl alcohol, with preference for cetyl alcohol. Itis also possible if desired for mixtures of fatty alcohols to bepresent.

The triglyceride is glycerol with its three hydroxyl groups esterifiedby carboxylic acids. The carboxylic acids are preferably monobasiccarboxylic adds with 8 to 22 carbon atoms, preferably naturallyoccurring carboxylic acids. It is possible in this case for thecarboxylic acids to be different or, preferably, identical. Exampleswhich may be mentioned are tristearate, tripalmitate and, particularlypreferably, trimyristate (these triglycerides are commercially availableunder the name Dynasan 118, 116 and 114 respectively). It is alsopossible if desired for mixtures of triglycerides to be present.

The fatty acid ester is the ester of an alcohol with a fatty acid. Thealcohol in this case is preferably a linear, saturated or unsaturatedprimary alcohol with 10–30, preferably with 12 to 18, carbon atoms. Thefatty acid is preferably a monobasic carboxylic acid with 8 to 22, inparticular 12 to 18, carbon atoms, preferably a naturally occurringcarboxylic acid. Fatty acid esters preferred according to the inventionhave a melting point above 30° C. Examples of fatty acid esters whichmay be mentioned are cetyl palmitate, which is commercially availablefor example under the name Cutina® CP. It is also possible if desiredfor mixtures of fatty acid esters to be present.

The solid paraffin is preferably paraffinum solidum (ceresin). It isalso possible alternatively to use ozokerite, for example. It is alsopossible if desired to use mixtures.

The partial glyceride is according to the Invention glycerol in whichone or two hydroxyl groups are esterified by carboxylic acids. Thecarboxylic acids are preferably monobasic carboxylic acids with 8 to 22carbon atoms, preferably naturally occurring carboxylic acids, inparticular stearic acid, palmitic acid and myristic acid. It is possiblein this case for the carboxylic acids to be different or, preferably,the same. Examples which may be mentioned are glycerol monostearate,glycerol distearate and glycerol monopalmitate, glycerol dipalmitate. Itis also possible if desired for mixtures of partial glycerides to bepresent.

If desired, the mixtures in the individual active ingredient units mayinclude one or more other pharmaceutically suitable excipients. Othersuitable excipients which may be mentioned by way of example arepolymers, sterols and—in the case of acid-labile activeingredients—basic compounds.

Examples of polymers which may be mentioned are povidone (e.g. Kollidon®17, 30 and 90 from BASF), vinylpyrrolidone/vinyl acetate copolymer andpolyvinyl acetate. Others which may be mentioned are cellulose ethers[such as, for example, methylcellulose, ethylcellulose (Ethocel®) andhydroxypropylmethylcellulose], cellulose esters [such as celluloseacetate phthalate (CAP), cellulose acetate trimellitate (CAT),hydroxypropylmethylcellulose phthalate (HP50 and HP55) orhydroxypropylmethylcellulose acetate succinate (HPMCAS)], methacrylicacidimethyl methacrylate copolymer or methacrylic acid/ethylmethacrylate copolymer (Eudragit® L). The polymer is preferably povidoneor ethylcellulose. It is also possible if desired for mixtures ofpolymers to be present. It is possible by adding suitable polymers, forexample, to influence the pharmaceutical properties of the individualactive ingredient units (e.g. delivery of the active ingredient).Particularly preferred polymers according to the invention are povidoneor ethylcellulose.

The sterol is preferably a phytosterol or a zoosterol. Examples ofphytosterols which may be mentioned are ergosterol, stigmasterol,sitosterol, brassicasterol and campesterol. Examples of zoosterols whichmay be mentioned are cholesterol and lanosterol. It is also possible ifdesired for mixtures of sterols to be present.

Examples of suitable basic compounds are inorganic basic salts such asammonium carbonate and sodium carbonate, salts of fatty acids such assodium stearate, amines such as meglumine, di-, triethylamine andTRIS(2-amino-2-hydroxymethyl-1,3-propanediol) or fatty amines such asstearylamine. Stearylamine and sodium stearate may be mentioned aspreferred. The addition of basic compounds to the mixtures in theindividual units results, in the case of acid-labile active ingredients,in particularly stable preparations and prevents possiblediscolorations.

The proportion (in percent by weight) of active ingredient in theindividual active ingredient unit depends on the type of activeingredient and is advantageously 0.01–90%. The proportion of activeingredient is preferably 0.1–70%, particularly preferably 5–40%, inparticular 10–20%. The proportion of fatty alcohol in the individualactive ingredient unit is advantageously 10–70%, preferably 20–70%,particularly preferably 20–60% and in particular 30–60%. The proportionof triglyceride in the individual active ingredient unit isadvantageously 10–70%, preferably 20–70%, particularly preferably 20–60%and in particular 30–60%. The proportion of partial glyceride in theindividual active ingredient unit is advantageously 10–70%, preferably20–70%, particularly preferably 20–60% and in particular 30–60%. Theproport of fatty acid ester in the individual active ingredient unit isadvantageously 10–70%, preferably 20–70%, particularly preferably 20–60%and in particular 30–60%. The proportion of solid paraffin isadvantageously 10–70%, preferably 20–60% and in particular 30–60%. Ifpresent, the proportion of polymer in the individual active ingredientunit is expediently 1–25%, preferably 1–10%, particularly preferably5–10%. If present, the proportion of sterol is expediently 1–10%,preferably 1–5%. If present, the proportion of basic compound is0.05–5%, preferably 0.1–1%.

Preferred individual active ingredient units of the invention consist of2–70% active ingredient, 10–60% fatty alcohol, 10–60% solid paraffin and1–15% polymer. Further preferred individual active ingredient units ofthe invention consist of 2–70% active ingredient, 10–60% triglyceride,10–60% solid paraffin, 1–15% polymer. Other preferred individual activeingredient units of the invention consist of 2–70% active ingredient,10–60% fatty acid ester, 10–60% solid paraffin and 1–15% polymer.

In one embodiment, the invention relates to a preparation in which anactive ingredient is essentially uniformly distributed in an excipientmatrix composed of a mixture of at least one solid paraffin, a fattyalcohol, a fatty acid ester and a partial glyceride or triglycedde. Suchpreparations preferably consist of 0.05 to 25% active ingredient, 10 to70% solid paraffin, 5 to 80% fatty alcohol, 2 to 20% fatty acid esterand 5 to 80% triglyceride or partial glyceride. Such preparationsconsist, in particular, of 0.1 to 20% active ingredient, 15 to 65% solidparaffin, 5 to 70% fatty alcohol, 2 to 15% fatty acid ester and 5 to 20%70% triglyceride or partial glyceride. Such preparations particularlypreferably consist of 0.5 to 15% active ingredient, 15 to 60% solidparaffin, 5 to 50% fatty alcohol, 5 to 10% fatty acid ester and 10 to50% triglyceride or partial glyceride.

In another embodiment, the invention relates to a preparation in whichan active ingredient is essentially uniformly dispersed in an excipientmatrix composed of at least one fatty alcohol together with at least oneexcipient selected from the group of solid paraffin or polymer. Thepolymer is preferably ethylcellulose or povidones. Such preparationspreferably consist of 0.05 to 25% active ingredient, 20 to 90% fattyalcohol, 10 to 80% solid paraffin and/or 0.05 to 2% ethylcellulose. Suchpreparations consist in particular of 0.1 to 20% active ingredient, 25to 80% fatty alcohol, 10 to 70% solid paraffin and/or 0.1 to 1.5%ethylcellulose. Such preparations particularly preferably consist of 0.5to 15% active ingredient, 25 to 70% fatty alcohol, 10 to 60% solidparaffin and/or 0.2 to 1% ethylcellulose.

In the case of acid-labile active ingredients, in particular theacid-labile proton pump inhibitors, preferred individual activeingredient units of the invention consist of 2–70% active ingredient,10–60% fatty alcohol, 10–60% solid paraffin, 1–15% polymer and 0.1–2% ofa basic compound. Further preferred individual active ingredient unitsof the invention consist of 2–70% active ingredient, 10–60% triglyceide,10–60% solid paraffin, 1–15% polymer and 0.1–2% of a basic compound.Other preferred individual active ingredient units of the Inventionconsist of 2–70% active ingredient, 10–60% fatty acid ester, 10–60%solid paraffin, 1–15% polymer and 0.1–2% of a basic compound.Particularly preferred individual active ingredient units of theInvention consist of 5–40% active ingredient, 20–60% fatty alcohol,10–60% solid paraffin, 1–15% polymer and 0.1–1% of a basic compound.Further particularly preferred individual active ingredient units of theinvention consist of 5–40% active ingredient, 20–60% triglyceride,10–60% solid paraffin, 1–15% polymer and 0.1–1% of a basic compound.Other particularly preferred individual active ingredient units of theinvention consist of 5–40% active ingredient, 20–60% fatty acid ester,10–60% solid paraffin, 1–15% polymer and 0.1–1% of a basic compound.

Examples of active ingredient units of the invention contain 5–40%pantoprazole sodium sesquihydrate, 10–40% cetyl alcohol, 5–60% solidparaffin, 1–5% polymer and 0.1–0.2% of a basic compound. Furtherexamples of active ingredient units of the invention contain 540%pantoprazole sodium sesquihydrate, 10–40% glyceryl tripalmitate, 5–60%solid paraffin, 1–5% polymer and 0.1–0.2% of a basic compound. Otherexamples of active ingredient units of the invention contain 5–40%pantoprazole sodium sesqulhydrate, 10–40% glyceryl tripalmitate, 5–60%solid paraffin, 1–5% polymer and 0.1–0.2% of a basic compound. Stillother examples of active ingredient units of the invention contain10–20% pantoprazole sodium sesquihydrate, 20–40% triglyceride, 40–70%solid paraffin, 1–5% sterol and 0.05–0.1% of a basic compound.

The individual active ingredient units can be produced for example byspray drying or, preferably, by spray solidification, in particular alsoby spray prilling. Production is particularly preferably by prilling, inparticular by vibration prilling.

For the spray solidification or prilling expediently the matrixexcipients are liquefied to give a melt. The active ingredient isdissolved or dispersed in this solution, and the resulting solution ordispersion is sprayed or, preferably, prilled in a suitable apparatus. Adispersion of the active ingredient in a melt of the exciplents ispreferably used.

Spray solidification takes place in a manner known per se. A detaileddescription of this technique is to be found in P. B. Deasy,Microencapsulation and Related Drug Processes (1984).

The individual active ingredient units are particularly preferablyproduced by solidification from liquid phase by generating drops bymeans of vibrating nozzles and by solidifying the drops which areformed, after they have stabilized, by drying or cooling in a suitablemedium (preferably gaseous or liquid). The suitable medium may be, forexample, cooled gas such as air or nitrogen. Processes of this type andcorresponding apparatuses are disclosed in DE 27 25 924, EP 0 467 221,WO99/33555 and WO00/24382.

It is particularly preferred according to the invention in the prillingprocess for the liquid phase flowing to the nozzle to be kept at aconstant temperature. The solidification preferably takes place byinstantaneous cooling in a suitable cooling medium. In prilling,moreover, it is preferred for the liquid phase flowing to the nozzle,the vibrating nozzle and the drops formed by prilling to be kept at aconstant temperature until their spherical shape has stabilized, and forthe solidification of the drops after their stabilization to be carriedout instantaneously by cooling with a gaseous or liquid cooling medium.Systems suitable for prilling by means of vibrating nozzles aremarketed, for example, by Brace GmbH, Alzenau, Germany. It is possibleby means of prilling using vibrating nozzles to obtain the individualactive ingredient units in the form of microspheres with a narrowmonomodal particle size spectrum in the particle size range from 50 μmto 2 mm. The narrow monomodal particle size spectrum and the uniformspherical shape of the microspheres obtained in this way are expected toresult in a uniformly smooth surface, a uniform, defined delivery ofactive ingredient and, in relation to passage through the stomach in thecase of oral dosage forms (owing to the small particles), a behaviorlike that of a solution. The microspheres of the invention aredistinguished in particular by high stability, a release of activeingredient which can be controlled via the particle size and compositionof the matrix, good flow characteristics, good compressibility and auniform delivery of active ingredient. It is particularly worthy ofmention that the microspheres can be further processed to a large numberof pharmaceutical dosage forms without thereby losing a givenfunctionality (such as taste masking, resistance to gastric juice,slowing of release).

The microspheres are preferably monomodal microspheres with a particlesize range of 50–800 μm, preferably 50–500 μm, particularly preferably50–400 μm, in particular 50–200 μm.

The particle size of the active ingredient employed in the spray dryingor spray solidification, prilling or vibration prilling isadvantageously less than or equal to 100 μm, in particular less than 40μm. The particle size is preferably in the range 1–20 μm, particularlypreferably in the range 3–15 μm. Such a particle size can be achieved,for example, by grinding the active ingredient in a suitable mill.

The individual active ingredient units (preparations) of the inventioncan then be used as basis for producing the dosage forms of theinvention. Examples which may be mentioned are dosage forms of theinvention, to which the preparations can be processed, as suspensions,gels, tablets, coated tablets, multicomponent tablets, effervescenttablets, rapidly disintegrating tablets, powders in sachets, coatedtablets, capsules, solutions or else suppositories. Preferred dosageforms in this connection are oral dosage forms, in particular tablets.Particular preference is given to rapidly disintegrating tablets andeffervescent tablets. The excipients suitable for the desired dosageforms are familiar to the skilled worker on the basis of his expertknowledge. In the case of oral dosage forms it is surprisingly possibleto dispense with the enteric coating.

In the case of rapidly disintegrating tablets, suitable excipients are,in particular, those excipients which on oral intake of the tablet bringabout rapid disintegration of the tablets. Excipents which on oralintake of the tablet bring about rapid disintegration of the tabletpreferably comprise one or more substances selected from the group offillers and disintegrants. One or more other excipients from the groupof lubricants, flavors, flavoring substances and surface-activesubstances are preferably present in the rapidly disintegrating dosageform of the invention. Binders can also be present if desired. Therapidly disintegrating dosage form particularly preferably comprises amixture of at least one filler, one disintegrant and one lubricant.Fillers suitable according to the invention are, in particular, basicfillers such as calcium carbonate (e.g. MagGran® CC or Destab® 95) andsodium carbonate, sugar alcohols such as mannitol (e.g. Pearlitol® orParteck® M), sorbitol (e.g. Karion®), xylitol or maltitol, starches suchas corn starch, potato starch and wheat starch, microcrystallinecellulose, saccharides such as glucose, lactose, levulose, sucrose anddextrose. In a preferred development of the invention, the rapidlydisintegrating dosage form of the invention comprises as filler amixture of a basic filler (in particular calcium carbonate) and a sugaralcohol (in particular sorbitol or mannitol). Disintegrants suitableaccording to the invention are, in particular, insolublepolyvinylpyrrolidone (insoluble PVP, crospovidone), sodiumcarboxymethylstarch, sodium carboxymethylcellulose, alginic acid andstarches able to carry out the function of a disintegrant (e.g. Starch1500). Suitable lubricants which may be mentioned are sodium stearylfumarate, magnesium stearate, calcium stearate, stearic acid, talc andhighly disperse silica (Aerosil). Suitable surfac-active substanceswhich may be mentioned are sodium lauryl sulfate or Tween® 20, 60 or 80.Binders suitable according to the Invention are polyvinylpyrrolidone(PVP, Polyvidon® K25, 90) or mixtures of PVP with polyvinyl acetate(e.g. Kollidon® 64), gelatin, corn starch mucilage, preswollen starches(Starch 1500), hydroxypropylmethylcellulose (HPMC) orhydroxypropyl-cellulose (L-HPC).

The proportion (in percent by weight based on the finished tablet) offiller in the rapidly disintegrating tablet is advantageously from 1 to99% by weight. The proportion of filler is preferably from 30 to 95% byweight, and the proportion is very particularly preferably from 60 to85% by weight.

The proportion (in percent by weight based on the finished tablet) ofdisintegrant in the rapidly disintegrating tablet is usually from 1 to30% by weight. The proportion of disintegrant is preferably from 2 to15% by weight. The proportion of disintegrant is particularly preferablyfrom 5 to 10% by weight.

The proportion (in percent by weight based on the finished tablet) oflubricant in the rapidly disintegrating tablet is usually from 0.1 to 5%by weight. The proportion of lubricant is preferably from 0.3 to 3% byweight. The proportion of lubricant is particularly preferably from 0.5to 2% by weight.

The proportion (in percent by weight based on the finished tablet) ofindividual active ingredient units in the rapidly disintegrating tabletis usually from 1 to 90% by weight. The proportion of individual activeingredient units is preferably up to 70% by weight, in particular from10 to 50% by weight. The proportion is very particularly preferably from15 to 25% by weight.

The proportion (in percent by weight based on the finished tablet) ofbinder can be up to 10% by weight, and it can preferably be up to 5% byweight.

If desired, one or more flavoring substances (e.g. flavors orsweeteners) can additionally be present in the rapidly disintegratingtablet. This makes it possible, for example, to achieve an improvementof the taste of the rapidly disintegrating tablet. These substances areadded in conventional amounts.

The rapidly disintegrating tablet is produced by processes known to theskilled worker. The rapidly disintegrating tablet is preferably producedby

-   i) dry mixing of filler and/or disintegrant;-   ii) production of granules of filler and binder and mixing of the    granules with a disintegrant or-   iii) dry granulation (briqueting or compacting) of one or more    excipient components.

The individual active ingredient units ar subsequently admixed to themixtures obtained in i), ii) or iii) and then, if desired,flavors/flavoring substances and finally also one or more lubricants areadmixed. The mixture obtained in this way can be compressed in a tabletpress under conventional conditions.

Rapid disintegration of the tablet means according to the Inventiondisintegration of the tablet in about 60 seconds or less when the tabletis subjected to a disintegration test as described in the EuropeanPharmacopoeia (3rd edition, 1997) 2.9.1 disintegration time of tabletsand capsules.

In the case of solutions and suspensions, suitable excipients are, inparticular, those excipients which are normally used to producesolutions or suspensions. Particularly suitable according to theinvention are excipients with which it is possible to produce athickened base, such as thickeners. Examples of thickeners of theinvention are xanthan, substituted celluloses, polyvinylpyrrolidone(polyvidone types), sheet silicates, alginates or alginic acids. Alsopossible if desired is a mixture of two or more different thickeners.The proportion of thickener depends on the desired viscosity orconsistency intended for the solution or suspension ready for use. Asolution or suspension with a viscosity of less than 500 mPa.s(determined with a rotational viscometer) is particularly preferred. Theproportion of xanthan, based on the solution or suspension ready foruse, is usually from 0.1 to 1% by weight. The proportion of substitutedcelluloses depends on the viscosity levels of the celluloses and isusually from 0.1 to 10% by weight based on the solution or suspensionready for use. Examples of substituted celluloses of the invention whichmay be mentioned are carboxymethylcellulose, ethylcellulose ormethylcellulose or hydroxypropylcellulose. The proportion ofpolyvinylpyrrolidone (polyvidone types) is normally from 0.1 to 10% byweight based on the solution or suspension ready for use. Sheetsilicates such as the Veegum or bentonites can be employed alone or incombination with water-soluble thickeners. The total proportion ofthickener is then advantageously from 0.1 to 7% by weight based on thesolution or suspension ready for use. Alginates and alginic acid areusually added in a proportion of from 0.1 to 10% by weight based on thesolution or suspension ready for use. Further pharmaceutical excipientspreferably employed are insoluble, crosslinked polyvinylpyrrolidone(crospovidones) and microcrystalline cellulose. It is observed in thiscase that a loose sediment forms and prevents agglomeration of theindividual active ingredient units. The ratio of crospovidones to theindividual active ingredient units is advantageously from 1:1 to 0.5:1(based on weight). Microcrystalline cellulose, which is normallyemployed in a proportion of from 0.5 to 5% by weight based on thesolution or suspension ready for use, is likewise suitable for thispurpose. The proportion of individual active ingredient units in thesolution or suspension ready for use is usually according to theinvention from 1 to 20% by weight based on the solution or suspensionready for use, preferably 1 to 15% by weight and very preferably 5 to10%. Water is preferably used as solvent or dispersant for the solutionor suspension.

Other suitable excipients which may be present in the solution orsuspension of the invention are, for example, flavoring substances (suchas flavors and sweeteners), buffer substances, preservatives or elseemulsifiers. Flavors are usually added in a proportion of from 0.05 to1% by weight. Other flavoring substances by way of example are acidssuch as citric acid, sweeteners such as saccharin, aspartame, cyclamatesodium or maltol, which are added according to the desired result.Examples of emulsifiers are lecithins, sodium lauryl sulfate, Tweens® orSpans, which are normally added in a proportion of from 0.01 to 1% byweight. Preservatives such as benzoic acid, salts of benzoic acid,methyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, sorbic acid or saltsthereof are preferably also added. The proportion depends on thepreservative used and is normally from 0.1 to 4% by weight based on thesolution or suspension ready for use.

The solution or suspension of the invention is produced by techniquesknown to the skilled worker. If a powder for reconstitution is to beproduced, preferably a mixture of the individual active ingredient unitswith the thickener and, where appropriate, further excipients isproduced. This powdered mixture for reconstitution is then mixed with asuitable amount of water immediately before administration. Solution orsuspension ready for use is normally produced by introducing theindividual active ingredient units into a dispersion of the thickenerand, where appropriate, of additives in water or, alternatively, byintroducing the thickener into a dispersion of the individual activeingredient units in water.

In a preferred embodiment, the invention relates to rapidlydisintegrating tablets or solutions or suspension which comprisepreparations of the invention with PDE inhibitors as active ingredients.Preferred PDE inhibitors in this case are roflumilast and pumafentrine.

The dosage forms of the invention can be employed for the treatment andprevention of all diseases which are regarded as treatable orpreventable by use of the particular active ingredient. The dosage formscontain the particular active ingredient in the dose usual for treatingthe particular disease.

The production of dosage forms and preparations of the invention isdescribed by way of example below. The following examples illustrate theinvention in detail without restricting it.

EXAMPLES Production of the Preparations (Active Ingredient Units)Example 1

50 g of solid paraffin, 34.9 g of cetyl alcohol and 0.1 g ofstearylamine are converted into a clear melt. 5.0 g of povidone isdissolved in the clear melt. At a temperature between 56–60° C., 10.0 gof pantoprazole sodium sesquihydrate is added and suspendedhomogeneously. The suspension is prilled in the molten state, and thedrops thus produced are solidified in a cooling zone.

Example 2

55 g of solid paraffin, 30.9 g of cetyl alcohol and 0.1 g ofstearylamine are converted into a clear melt. 4.0 g of povidone isdissolved in the clear melt. At a temperature between 56–60° C., 10.0 gof pantoprazole magnesium is added and suspended homogeneously. Thesuspension is prilled in the molten state, and the drops thus producedare solidified in a cooling zone.

Example 3

45.0 g of solid paraffin, 33.8 g of cetyl alcohol, 1.0 g of β-sitosteroland 0.2 g of stearylamine are converted into a clear melt. 1.0 g ofpovidone and 4.0 g of ethylcellulose are dissolved in the clear melt. Ata temperature between 56–60° C., 15.0 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state, and the drops thus produced are solidifiedin a cooling zone.

Example 4

52.0 g of solid paraffin, 30.3 g of cetyl alcohol and 0.2 g ofstearylamine are converted into a clear melt. 5.0 g of povidone isdissolved in the clear melt. At a temperature between 56–60° C., 12.5 gof pantoprazole sodium sesquihydrate is added and suspendedhomogeneously. The suspension is prilled in the molten state, and thedrops thus produced are solidified in a cooling zone.

Example 5

77.2 g of cetyl alcohol and 0.3 g of stearylamine are converted into aclear melt. 10.0 g of povidone is dissolved in the clear melt. At atemperature between 56–60° C., 12.5 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state, and the drops thus produced are solidifiedin a cooling zone.

Example 6

47 g of solid paraffin, 40 g of glyceryltripalmitate (Dynasan 116, fromHüls) and 3 g of sitosterol ar converted into a clear melt at 100° C.and cooled to 55–60° C. 10 g of lansoprazole are added and suspendedhomogeneously. The suspension is put in the feed container of a prillingunit (from Brace) and prilled from a 200 μm nozzle at about 0.1 bar. Aperiodic vibration with a frequency of about 390 Hz is transmitted tothe nozzle head during this. The resulting drops are solidified in acooling zone with air at a temperature of −30° C.

Example 7

15 g of glyceryl trimyristate (Dynasan 114), 15 grams of glyceryltripalmitate (Dynasan 116), 50 grams of solid paraffin and 5 g ofcholesterol are converted into a clear melt at about 100° C. The clearmelt is cooled to about 55–65° C. 15 g of rabeprazole are added, theactive ingredient is uniformly dispersed, and the homogeneous suspensionis priled as in example 6.

Example 8

10 g of glyceryl tripalmitate (Dynasan 116), 209 of glyceryltrimyristate (Dynasan 114), 529 of solid paraffin and 3 g of sitosterolare converted into a clear melt at about 100° C. The clear melt iscooled to 55–65° C. 15 g of omeprazole Mg are added and suspendedhomogeneously. The suspension is put in the feed container of a prillingunit (from Brace) and prilled through a 200 μm nozzle at 90 mbar. Aperiodic vibration with a frequency of about 400 Hz is transmitted tothe nozzle head during this. The resulting drops are solidified with airat a temperature of −30° C. in a cooling zone.

Example 9

18 g of tristearin, 60 g of solid paraffin and 5 g of cholesterol areconverted into a clear melt. The clear melt is cooled to 56–60° C. 10 gof pantoprazole sodium sesquihydrate are introduced and homogeneouslydispersed. The suspension is prilled in the molten state in a prillingunit (from Brace) with vibrating nozzles, and the resulting drops aresolidified in a cooling zone.

Example 10

18 g of cetyl palmitate, 40 g of solid paraffin and 2 g of cholesterolare converted into a clear melt. The clear melt is cooled to 56–60° C.10 g of pantoprazole sodium sesquihydrate are introduced and homogenizeduntil a uniform suspension results. The suspension is prilled in themolten state in a prilling unit (from Brace) with vibrating nozzles, andthe resulting drops are solidified in a cooling zone.

Example 11

50 g of solid paraffin and 40 g of cetyl palmitate (Cutina® CP) areconverted into a clear melt at 100° C. The dear melt is cooled to 50–60°C. 10 g of pantoprazole sodium sesquihydrate are introduced andsuspended homogeneously. The suspension is prilled in the molten statein a prilling unit (from Brace) with vibrating nozzles (200 μm nozzle),and the resulting drops are solidified in a cooling zone.

Example 12

50 g of solid paraffin and 40 g of cetyl alcohol are converted into aclear melt at 100° C. The clear melt is cooled to 50–60° C. 10 g ofpantoprazole sodium sesquihydrate are introduced and suspendedhomogeneously. The suspension is prilled in the molten state in aprilling unit (from Brace) with vibrating nozzles (200 μm nozzle), andthe resulting drops are solidified in a cooling zone.

Example 13

50 g of solid paraffin and 40 g of glyceryl trimyristate are convertedinto a clear melt at 100° C. The clear melt is cooled to 50–60° C. 10 gof pantoprazole sodium sesquihydrate are introduced and suspendedhomogeneously. The suspension is prilled in the molten state in aprilling unit (from Brace) with vibrating nozzles (200 μm nozzle), andthe resulting drops are solidified in a cooling zone.

Example 14

47 g of solid paraffin, 40 g of glyceryl tripalmitate (Dynasan 116, fromHuls) and 3 g of sitosterol are converted into a clear melt at 100° C.and cooled to 55–60° C. 10 g of lansoprazole are added and suspendedhomogeneously. The suspension is put into the feed container of aprilling unit (from Brace) and prilled from a 200 μm nozzle at about 0.1bar. A periodic vibration with a frequency of about 390 Hz istransmitted to the nozzle head during this. The resulting drops aresolidified in a cooling zone with air at a temperature of −30° C.

Example 15

30 g of tristearin, 60 g of solid paraffin and 4 g of sitosterol and0.07 gstearylamine are converted into a clear melt. The clear melt iscooled to 56–60° C. 15 g of pantoprazole sodium sesquihydrate areintroduced and homogeneously dispersed. The suspension is prilled in themolten state in prilling unit (from Brace) with vibrating nozzles, andthe resulting drops are solidified in a cooling zone.

Example 16

17.5 g of glyceryl trimyristate (Dynasan 114), 67.59 of solid paraffinand 5 g of cholesterol are converted into a clear melt at about 100° C.The clear melt is cooled to about 55–65° C. 10 g of pantoprazole areadded, and the active ingredient is uniformly dispersed, and thehomogeneous suspension is prilled as in example 6.

Example 17

98 g of cetyl alcohol and 1 g of solid paraffin are converted into aclear melt at about 90° C. 1 g of roflumilast is added, and the mixtureis stirred until it is a clear solution. The clear melt is prilled atabout 70° C. in a suitable vibration prilling unit (conditions: 200 or350 μm nozzle, pressure 100 to 170 mbar, frequency about 1 kHz).

Example 18

90 g of glyceryl monostearate are converted into a clear melt at about90° C. 10 g of roflumilast is added, and the mixture is stirred until itis a clear solution. The clear melt is prilled at about 70° C. in asuitable vibration prilling unit (conditions: 200 or 350 μm nozzle,pressure 100 to 170 mbar, frequency about 1 kHz).

Example 19

88 g of glyceryl myristate and 11.2 g of paraffin are converted into aclear melt at about 90° C. 0.8 g of roflumilast is added, and themixture is stirred until it is a clear solution. The clear melt isprilled at about 70° C. in a suitable vibration prilling unit(conditions: 200 or 350 μm nozzle, pressure 100 to 170 mbar, frequencyabout 1 kHz).

Example 20

96 g of cetyl alcohol and 2 g of ethylcellulose are converted into aclear melt at about 90° C. 2 g of roflumilast is added, and the mixtureis stirred until it is a clear solution. The clear melt is prilled atabout 70° C. in a suitable vibration prilling unit (conditions: 200 or350 μm nozzle, pressure 100 to 170 mbar, frequency about 1 kHz).

Example 21

84 g of glyceryl monostearate and 8 g of paraffin are converted into aclear melt at about 90° C. 8 g of roflumilast is added, and the mixtureis stirred until it is a clear solution. The clear melt is prilled atabout 70° C. In a suitable vibration prilling unit (conditions: 200 or350 μm nozzle, pressure 100 to 170 mbar, frequency about 1 kHz).

Example 22

59 g of glyceryl monostearate, 20 g of cetyl palmitate and 20 g ofparaffin are converted into a clear melt at about 90° C. 1 g ofroflumilast is added, and the mixture is stirred until it is a dearsolution. The clear melt is prilled at about 70° C. in a suitablevibration prilling unit (conditions: 200 or 350 μm nozzle, pressure 100to 170 mbar, frequency about 1 kHz).

Example 23

50 g of cetyl alcohol, 5 g of glyceryl monostearate, 10 g of cetylpaimitate, 10 g of glyceryl tristearate and 24.5 g of paraffin areconverted into a dear melt at about 90° C. 0.5 g of roflumilast isadded, and the mixture is stirred until it is a clear solution. Theclear melt is prilled at about 70° C. in a suitable vibration prillingunit (conditions: 200 or 350 μm nozzle, pressure 100 to 170 mbar,frequency about 1 kHz).

Example 24

70 g of cetyl alcohol and 29.5 g of paraffin are converted into a clearmelt at about 90° C. 0.5 g of roflumilast is added, and the mixture isstirred until it is a clear solution. The clear melt is prilled at about75 to 80° C. in a suitable vibration prilling unit (conditions: 200 or350 μm nozzle, pressure 100 to 170 mbar, frequency about 1 kHz).

Example 25

97.7 g of cetyl alcohol and 0.3 g of ethylcellulose are converted into aclear melt at about 90° C. 2 g of pumafentrine is added, and the mixtureis stirred until it is a clear solution. The clear melt is prilled atabout 75 to 80° C. in a suitable vibration prilling unit (conditions:200 or 350 μm nozzle, pressure 100 to 170 mbar, frequency about 1 kHz).

Example 26

69 g of cetyl alcohol, 5 g of cetyl palmitate, 10 g of glyceryltristearate and 15 g of paraffin are converted into a clear melt atabout 90° C. 1 g of pumafentrine is added, and the mixture is stirreduntil it is a clear solution. The clear melt is prilled at about 70° C.in a suitable vibration prilling unit (conditions: 200 or 350 μm nozzle,pressure 100 to 170 mbar, frequency about 1 kHz).

Example 27

40 g of cetyl alcohol, 7 g of cetyl palmitate, 33 g of glyceryltristearate and 15 g of paraffin are converted into a clear melt atabout 90° C. 5 g of(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridineare added, and the mixture is stirred until it is a clear solution. Theclear melt is prilled at about 70° C. in a suitable vibration prillingunit (conditions: 200 or 350 μm nozzle, pressure 100 to 170 mbar,frequency about 1 kHz).

Example 28

41 g of cetyl alcohol, 7 g of cetyl palmitate, 33 g of glyceryltristearate and 17 g of paraffin are converted into a clear melt atabout 90° C. 2 g of(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridineare added, and the mixture is stirred until it is a clear solution. Theclear melt is prilled at about 70° C. in a suitable vibration prillingunit (conditions: 200 or 350 μm nozzle, pressure 100 to 170 mbar,frequency about 1 kHz).

Example 29

41 g of cetyl alcohol, 7 g of cetyl palmitate, 33 g of glyceryltristearate and 17 g of paraffin are converted into a clear melt atabout 90° C. 2 g of(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridineare added, and the mixture is stirred until it is a clear solution. Theclear melt is prilled at about 70° C. in a suitable vibration prillingunit (conditions: 200 or 350 μm nozzle, pressure 100 to 170 mbar,frequency about 1 kHz).

Example 30

38 g of glyceryl tripaImitate, 2 g of cholesterol and 59.5 g of paraffinare converted into a clear melt at about 100° C. Then 0.5 g ofciclesonide is added, and the melt is prilled at about 75° C. in asuitable vibration prilling unit (conditions: 100 μm nozzle, pressure100 to 170 mbar, frequency about 1.3 kHz).

Example 31

38 g of glyceryl tripalmitate, 10 g of cetyl alcohol, 2 g of cholesteroland 49.5 g of paraffin are converted into a clear melt at about 100° C.Then 0.5 g of ciclesonide is added, and the melt is prilled at about 75°C. in a suitable vibration prilling unit (conditions: 100 μm nozzle,pressure 100 to 170 mbar, frequency about 1.3 kHz).

Example 32

36 g of cetyl alcohol, 60 g of glyceryl monostearate and 2 g ofvinylpyrollidone/vinyl acetate copolymer and 2 g of pumafentrine areconverted into a clear melt. The clear melt is prilled at about 60° C.with a nozzle and the resulting drops are solidified by cooling.

Example 33

30 g glyceryl trimyristate, 45 g glyceryl monostearate and 20 g cetylalcohol are converted into a clear melt. 5 g of roflumilast is added,and homogeneously dispersed. The melt is prilled at about 65° C. and theresulting drops are solidified in cooling zone.

Example 34

80 g cetostearyl alcohol, 0.5 g sodium stearate, 5 g ofvinylpyrollidone/vinyl acetate copolymer and 12.5 g of glyceroltrimyristate are converted into a clear melt at about 70° C. 2 g of(7R,8R,9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridineis added at 60° C. and dispersed homogeneously. The mixture is prilledat 60° C. and the resulting drops solidified in a cooling zone.

Example 35

20 g glyceryl trimyristate, 14.5 g glyceryl monostearate, 60 g cetylalcohol and 5 g vinylpyrollidone/vinyl acetate copolymer are convertedinto a clear melt at 70° C. 0.5 g of ciclesonide is added andhomogeneously dispersed. The dear melt is prilled and the resultingdrops are solidified in cooling zone.

Example 36

56.7 g of cetyl alcohol, 3 g of vinylpyrollidone/vinyl acetatecopolymer, 15 g of solid paraffin, 15 g of cetyl palmitate and 0.1 g ofsodium stearate are converted into a clear melt. At a temperaturebetween 56–60° C., 10.0 g of pantoprazole sodium sesquihydrate is addedand suspended homogeneously. The suspension is prilled in the moltenstate at 60° C. and the drops thus produced are solidified in a coolingzone.

Example 37

46.7 g of cetostearylic alcohol, 4 g of vinylpyrollidone/vinyl acetatecopolymer, 23 g solid paraffin, 0.3 g of sodium stearate and 1 gsitosterol are converted into a clear melt. At a temperature between60–65° C. 10.0 g of pantoprazole sodium sesquihydrate is added andsuspended homogeneously. The suspension is prilled in the molten stateat 60 to 65° C. and the drops thus produced are solidified in a coolingzone.

Example 38

39.9 g of cetyl alcohol, 3 g of vinylpyrollidone/vinyl acetatecopolymer, 20 g of cetyl palmitate, 2 g cholesterol, 17 g solid paraffinand 0.1 g of sodium stearate are converted into a clear melt. At atemperature between 56–60° C., 18.0 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state at 60° C. and the drops thus produced aresolidified in a cooling zone.

Example 39

47.9 g cetostearylic alcohol, 2 g of vinylpyrollidone/vinyl acetatecopolymer, 25 g of cetyl palmitate, 1 g sitosterol, 15 g solid paraffinand 0.1 g of sodium stearate are converted into a clear melt. At atemperature between 56–60° C., 15.0 g of pantoprazole sodiumsesquihydrate is added and suspended homogeneously. The suspension isprilled in the molten state at 60° C. and the drops thus produced aresolidified in a cooling zone.

The preparations obtained as in examples 1–39 have a particle size inthe range 50–700 μm. It is possible, for example by varying theprocessing conditions, to obtain larger particles.

Production of the Dosage Forms

Example A

134.7 g of mannitol, 30 g of Kollidon® 30 and 20 g of xanthan are mixeddry. The mixture is granulated with water in a fluidized bed granulator.Granules with a particle size of 0.8–1.5 mm are obtained and are mixedwith the preparation (125 g) obtained as in example 1. The mixtureobtained in this way is packed into bags (sachet) or—if requiredtogether with further tablet exciplents—compressed to tablets in amanner known to the skilled worker.

Example B

An amount which corresponds to 22.6 mg of pantoprazole magnesium of thepreparation obtained as in example 2 is mixed with 500 mg of lactose and100 mg of xanthan. The mixture is then mixed with flavoring substances(sweetener, flavor) depending on the individual sense of taste, andthereafter packed in a bag (sachet). A suspension for oral intake isobtained by dissolving the contents of a bag in a glass of water withstirring.

Example C

An amount corresponding to 45.2 mg of pantoprazole sodium sesquihydrateof the preparation from example 3 is mixed with the appropriate amountof lactose. This mixture is mixed with a mixture of citric acid andsodium carbonate. After addition of a suitable lubricant (for examplesodium stearyl fumarate) and addition of one or more suitable flavoringsubstances, the resulting mixture is compressed directly (withoutfurther granulation) to an effervescent tablet. A suspension for oralintake is obtained by dissolving a tablet in a glass of water.

Example D

An amount corresponding to 45.2 mg of pantoprazole sodium sesquihydrateof the preparation of example 4 is mixed with lactose to improve theflow properties. The mixture is packed together with suitable otheractive ingredients (for example amoxicillin or NSAIDs in usual dosageforms) into hard gelatin capsules of a suitable size.

Example E

300 mg of lactose are added to an amount corresponding to 30 mg oflansoprazole of the preparation of example 6. The two components aremixed with citric acid and sodium carbonate and, after addition of asuitable lubricant (for example sodium stearyl fumarate) and addition ofsuitable flavoring substances, compressed to a tablet.

Example F

450 mg of sucrose and 300 mg of xanthan are added to an amountcorresponding to 30 mg of rabeprazole of the preparation of example 7.The components are mixed, and masking flavors are added. The granulesare packed into sachets. The contents of a sachet can be put into aglass of water and is ready for use after stirring.

Example G

60 grams of the preparation of example 8 are mixed dry with 140 grams ofmannitol, 30 grams of Kollidon 30 and 20 grams of xanthan. The mixtureis granulated with water in a fluidized bed granulator. Granules with aparticle size of 0.8–1.5 mm are obtained. The mixture obtained in thisway is packed into bags (sachets).

Example H

140 g of mannitol, 30 g of Kollidon 30 and 20 g of xanthan are mixed dryand then granulated with water in a fluidized bed granulator. Theresulting granules are screened. The screen fraction from 0.8 to 1.5 mmis mixed with 6.98 g of preparation from example 18 and packed into bags(sachets).

Example I

5 g of a preparation of example 17 are mixed with 50 g of lactose and 8g of xanthan. Sweeteners and flavors are added to the mixture, and it ispacked into bags (sachets). A suspension ready for drinking is obtainedby stirring a bag into a glass of water.

Example J

12.5 mg of a preparation from example 19 are mixed with the appropriateamount of lactose. This mixture is mixed with a mixture of sodiumcarbonate and citric acid. After addition of a suitable lubricant (forexample sodium stearyl fumarate) and addition of flavoring substancesand sweeteners, the mixture obtained in this way is directly compressedto an effervescent tablet. Placing the tablet in a glass of waterresults, after dissolution thereof, in a suspension ready for drinking.

Example K

100 mg of a preparation from example 20 are mixed with 1.9 g of lactoseand packed into 10 hard gelatin capsules.

Example L

500 mg of a preparation from example 21 are granulated with water with15 g of mannitol and 4 g of Kollidon. The granules sufficient for 100single doses are packed into capsules.

Example M

1 g of a preparation from example 26 are mixed with 0.2 g of xanthan,0.1 g of saccharin sodium, 1.5 g of mannitol and 0.3 g of dry orangeflavor and packed into a sachet. The suspension after stirring intoabout 100 ml of water is ready for use.

Example N

200 mg of a preparation from example 27 are mixed with 670 mg ofDestab95 SE, 2270 mg of Pearlitol 300 DC and 50 mg of crospovidone in afree-fall mixer. 10 mg of magnesium stearate are then added through ascreen. This mixture is pressed in a tablet press.

Example O

40 mg of a preparation from example 30 are mixed with 500 mg of MagGranCC, 200 mg of Karion and 70 mg of crospovidone in a free-fall mixer. 12mg of magnesium stearate are then added through a screen, followed bybrief mixing again. The mixture obtained in this way is compressed in atablet press.

Example P

1. Preparation from example 22  12.500 mg 2. Lactose-1-hydrate 172.125mg 3. Corn starch  45.000 mg 4. Polyvidon ® 25  12.500 mg 5. Polyvidoneinsoluble  12.500 mg 6. Flavors  2.500 mg 7. Aspartame  0.375 mg 8.Citric acid  2.500 mg 9. Magnesium stearate  2.500 mg Total 262.500 mg

Production: 2. and 3. are granulated with a solution of 4. The granulesare dried and screened. 5. is admixed using a free-fall mixer, and then6., 7. and 8. are incorporated. 1. is admixed and finally 9. is brieflyadmixed using a free-fall mixer. The mixture obtained in this way iscompressed in a tablet press.

Example Q

1. Preparation from example 23  25.000 mg 2. Cellactose ® 229.625 mg 3.Sodium carboxymethylstarch  12.500 mg 4. Flavors  2.500 mg 5. Aspartame 0.375 mg 6. Citric acid  2.500 mg 7. Magnesium stearate  2.500 mg Total275.000 mg

Production: 2. and 3. are mixed. 4., 5. and 6. are incorporated. 1. isadmixed and finally 9. is briefly admixed using a free-fall mixer. Themixture obtained in this way is compressed in a tablet press.

Example R

1. Preparation from example 22  12.500 mg 2. Lactose-1-hydrate  49.660mg 3. Corn starch  13.390 mg 4. Polyvidon ® K 90  1.300 mg 5. Mannit 32.240 mg 6. PVP insoluble  12.890 mg 7. Flavors  0.330 mg 8. Magnesiumstearate  1.650 mg Total 123.960 mg

Production: 2. and 3. are granulated with a solution of 4. The granulesare dried and screened. 1., 5., 6. and 7. is admixed using a free-fallmixer, and then 8. is briefly admixed using a free-fall mixer. Themixture obtained in this way is compressed in a tablet press.

Example S

1. Preparation from example 22  12.500 mg 2. Lactose-1-hydrate  70.300mg 3. Potatoe starch  19.480 mg 4. Corn starch  2.370 mg 5. sodiumcarboxymethylstarch  1.900 mg 6. Flavors  0.330 mg 7. Magnesium stearate 0.950 mg Total 105.930 mg

Production: 2. and 3. are granulated with a solution of 4. The granulesare dried and screened. 1., 5. and 6. is admixed using a free-fallmixer, and then 7. is briefly admixed using a free-fall mixer. Themixture obtained in this way is compressed in a tablet press.

1. A preparation in which an active ingredient which isN-(3.5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide(INN: roflumilast), the N-oxide of roflumilast or a pharmacologicallysuitable salt of roflumilast or of its N-oxide is essentially uniformlydispersed or dissolved in an excipient matrix comprising one or moreexcipients selected from the group consisting of a fatty alcohol, atriglyceride, a partial glyceride and a fatty acid ester, wherein thepreparation is in the form of microspheres.
 2. The preparation accordingto claim 1, further comprising one or more additional otherpharmaceutically suitable excipients are present in the excipientmatrix.
 3. The preparation according to claim 2, further comprising oneor more other excipients selected from the group consisting of polymersand sterols are present in the excipient matrix.
 4. The preparationaccording to claim 1, wherein the excipient matrix comprises one or moreexcipients selected from the group consisting of a fatty alcohol, atriglyceride and a partial glyceride.
 5. The preparation according toclaim 1, wherein the excipient matrix is composed of at least one solidparaffin together with one or more excipients selected from the groupconsisting of a fatty alcohol, a triglyceride, a partial glyceride and afatty acid ester.
 6. The preparation according to claim 5 in which theactive ingredient is i) present in a matrix composed of a mixturecomprising at least one fatty alcohol and at least one solid paraffin,ii) present in a matrix composed of a mixture comprising at least onetriglyceride and at least one solid paraffin, iii) present in a matrixcomposed of a mixture comprising at least one partial glyceride and atleast one solid paraffin or iv) present in a matrix composed of amixture comprising at least one fatty acid ester and at least one solidparaffin.
 7. The preparation according to claim 1, wherein themicrospheres have a particle size in the range of 50–500 μm.
 8. Thepreparation according to claim 1, wherein the microspheres have aparticle size in the range of 50–400 μm.
 9. The preparation according toclaim 1, wherein the partial glyceride is selected from the groupconsisting of glycerol monostearate, glycerol distearate, glycerolmonopalmitate, glycerol dipalmitate and mixtures thereof.
 10. Thepreparation according to claim 9, wherein the partial glyceride isglycerol monostearate.
 11. The preparation according to claim 1, whereinthe fatty alcohol is selected from the group consisting of cetylalcohol, myristyl alcohol, lauryl alcohol, stearyl alcohol and mixturesthereof.
 12. The preparation according to claim 11, wherein the fattyalcohol is cetyl alcohol.
 13. The preparation according to claim 1,obtainable by prilling a solution or dispersion of the active ingredientin the melt of the excipients using a vibrating nozzle.
 14. Apharmaceutical dosage form comprising a preparation as claimed in claim1 further comprising one or more additional pharmaceutical excipients.